A Complete Guide to Choosing Resins for SPPS (Solid-Phase Peptide Synthesis): Fmoc/Boc Routes, C-Terminal Acid/Amide, and a Key-Parameter Navigator

What is Solid-Phase Peptide Synthesis (SPPS)?

Solid-Phase Peptide Synthesis (SPPS) is a method in which a growing peptide chain is covalently “tethered” to insoluble resin beads, and the synthesis proceeds through repeated cycles of “deprotection → coupling one amino acid → washing.” Because the peptide remains attached to the resin throughout the process, after each reaction step you can simply filter and wash to remove excess reagents and byproducts—rather than performing complicated purification after every step as in solution-phase synthesis. This core concept was first systematically proposed and validated by Merrifield.

Analogy: It’s like fixing one end of a necklace to a “handle” (the resin bead). Each time, you only need to string on the next bead (amino acid), and then wash away the excess materials.

How is SPPS carried out step by step?

Using today’s most common Fmoc-SPPS as an example (widely used in both labs and industry):

Step A: Attach the “first amino acid” to the resin

(1) Typically, the C-terminus of the first amino acid is attached to the resin through a linker, so the peptide chain generally grows from C → N. Many common amide/acid resins explicitly state that they are “loaded with the C-terminal residue.”

(2) In practice, there are two common ways to start:

a) Use a preloaded resin (e.g., preloaded Wang or Rink Amide resin) to skip the loading step;

b) Use a loadable resin to load the first amino acid yourself (e.g., 2-CTC, chloromethyl resin, etc.), which requires specific bases/activators and careful condition control.

Step B: Deprotect (restore N-terminus reactivity)

(1) The N-terminus protected by Fmoc is commonly removed under basic conditions such as piperidine/DMF (one of the standard operational paradigms).

(2) Note: A common condition is ~20% piperidine in DMF (or alternative systems such as 4-methylpiperidine, piperazine, etc.). Certain sequences/sites (e.g., Asp–X, Gly–Pro) are more prone under basic treatment to side reactions such as aspartimide formation and diketopiperazine (DKP) formation, which require formulation/strategy adjustments to mitigate. DKP often occurs at the dipeptide stage, especially during Fmoc deprotection; the risk is higher when the first two residues include Pro/Gly and the peptide is anchored via a benzyl alcohol–type linker (e.g., Wang). Switching to a trityl-type support (e.g., 2-CTC) or adjusting the deprotection/initial loading strategy can reduce DKP risk.

Step C: Couple the next amino acid

(1) Use coupling reagents to attach the next protected amino acid to the chain’s N-terminus.

Step D: Wash (the key to SPPS efficiency)

(1) After the reaction, wash directly to remove excess amino acid, coupling reagents, and byproducts—the peptide remains on the resin.

Step E: Repeat cycles until the sequence is complete

Step F: Final cleavage + global deprotection

(1) Cleavage: release the peptide from the resin/linker.

(2) Global side-chain deprotection: remove side-chain protecting groups (e.g., tBu/Trt/Pbf, etc.) to obtain the final peptide product.

(3) Note: Mild cleavage is intended to obtain protected fragments/intermediates. If the goal is the final product peptide, one typically uses a TFA cocktail to achieve “cleavage + global deprotection” in one pot. Therefore, resin/linker selection not only determines whether the C-terminus is an acid or an amide, but also whether you are better suited to mild cleavage to obtain protected fragments versus standard TFA one-pot global deprotection.

What are “commonly used resins for SPPS”?

Here, “resin” refers to insoluble polymer beads (microspheres) whose surfaces bear reactive functional groups. The peptide chain is attached via a linker. The resin’s roles can be understood as:

1. Anchoring the peptide: makes it possible to “wash away everything excess,” greatly simplifying operations (the essence of SPPS).

2. A micro-reactor: each bead is like a tiny reaction vessel; reagents must diffuse into the bead interior for reactions to proceed.

3. Determining the C-terminus form and cleavage mode: different linkers lead to peptides with C-terminal acids, amides, or other derivatives.

What are the common resins? (First, classify by “backbone material” into three major types)

A. Polystyrene-based (PS, usually low crosslinking)

(1) Classic, low cost, widely used; many common resins such as Wang and Rink Amide are PS-based.

(2) Descriptions often include “PS crosslinked with 1% DVB,” emphasizing that low crosslinking favors diffusion and swelling.

B. PEG–PS hybrid/composite (e.g., TentaGel)

(1) PEG is grafted onto PS to make the resin more polar and more suitable for certain sequences; TentaGel is often described as a copolymer with PEG grafted onto a PS matrix.

(2) Note: PEG–PS is a grafted/composite system. Different products can vary greatly in PEG attachment chemistry, grafting density, and stability. Under certain solvents or harsher processing conditions, discussions may arise regarding trace extractables or segment leaching. For applications sensitive to trace background, it is advisable to prioritize supplier data (COA/blank background validation) and to perform adequate pre-washing and blank controls.

C. Pure PEG-based (e.g., ChemMatrix)

(1) More hydrophilic, with stronger swelling and broader solvent compatibility; often used for difficult peptides that are longer, more hydrophobic, and more prone to aggregation. ChemMatrix is described as a 100% PEG resin, emphasizing swelling performance and stability in various solvents (even water, etc.).

(2) Regarding leaching: compared with graft-type PEG–PS, certain all-PEG network designs can, under some conditions, make it easier to achieve “fewer extractables/more controllable background.” In practice, this still depends on the specific product structure, batch, and use conditions. For high-sensitivity detection or trace-control scenarios, validate via blank cleavage and blank LC–MS.

What is the “relationship” between SPPS and resins?

Without resin, there is no “solid-phase” synthesis. Whether the resin choice is appropriate often directly determines whether a peptide can be built smoothly, whether it is pure, and whether it is easy to cleave.

More specifically:

(1) Resin = operational platform: enables “washing instead of purification” (the source of SPPS efficiency).

(2) Resin parameters = reaction environment: swelling, crowding at reactive sites, and diffusion rate all influence coupling completeness, deletion sequences, and crude purity.

(3) Linker = C-terminus and cleavage strategy: the same sequence can yield a C-terminal acid or a C-terminal amide simply by changing the linker.

What are the most important resin parameters, and what do they do?

① Loading / Substitution (mmol/g)

(1) What it is: the amount of reactive sites per gram of dry resin (commonly in mmol/g).

(2) What it affects: the theoretical maximum yield, and whether chains become too crowded.

(3) Why it matters:

(a) If loading is too high: sites are crowded; peptide chains are more likely to “pack together,” form aggregates/secondary structure, leading to incomplete coupling and more deletion sequences;

(b) If loading is lower: more favorable for long/difficult sequences (sacrificing yield per gram of resin for higher success rate and purity);

(c) Modern SPPS reviews and process guides often explicitly recommend lower loading for larger peptides or difficult sequences.

② Linker type (attachment arm / cleavage site)

(1) What it is: the chemical structure that “hangs” the peptide on the resin, determining how cleavage occurs and what the peptide C-terminus becomes.

(2) Most common “outcome types” (a highly practical selection dimension):

(a) C-terminal acid (peptide acid): e.g., Wang-type;

(b) Note: not all “acid resins” fall within the standard TFA cleavage window. Rink acid is a super acid-labile acid-terminating resin, enabling release of C-terminal carboxylic-acid peptides/protected fragments under milder conditions—but it is also more prone to premature detachment upon acid exposure during synthesis or handling. If the target is a conventional final acid peptide, Wang or 2-CTC is often preferred (more robust within standard cleavage windows).

(c) C-terminal amide (peptide amide): e.g., Rink Amide-type;

(d) Other C-terminal derivatives/fragment strategies: e.g., 2-CTC / SASRIN are more often used for C-terminal acids; Sieber Amide is more often used for C-terminal amides—commonly for mild cleavage to obtain protected fragments/special termini.

(3) Why it matters: whether you need an acid or an amide at the C-terminus is often determined by the linker from the very beginning and is difficult to “fix later.”

③ Swelling (swelling volume/capacity) and solvent compatibility

(1) What it is: how much the resin can swell in solvents such as DMF/DCM/MeOH/water, etc.

(2) What it affects: the resin must open like a “sponge” for reagents to diffuse in; poor swelling → slow diffusion → slow and incomplete reactions.

(3) Evidence and observations: PEG and pure-PEG resins (e.g., ChemMatrix) are often noted for better swelling across multiple solvents and improved performance for difficult peptides; references and studies discuss swelling differences between PS and ChemMatrix in different solvents.

④ Crosslinking and pore structure (porosity)

(1) What it is: how “tight” the resin network is.

(2) What it affects: lower crosslinking usually favors diffusion and swelling; higher crosslinking yields a harder bead but may limit diffusion. Many reviews/technical notes point out that peptide synthesis often favors low crosslinking for better diffusion and swelling.

⑤ Particle size / mesh size (bead size)

(1) What it is: the size of resin beads (e.g., 100–200 mesh, 200–400 mesh, etc.).

(2) What it affects:

(a) Smaller particles: shorter diffusion paths, faster and more complete reactions;

(b) But filtration is slower, and flowability/equipment clogging risk may increase.

(3) Why it matters: manual synthesis, automated synthesis, and scale-up may prefer different particle sizes.

⑥ Chemical stability / “leaching”

(1) What it is: whether the resin backbone decomposes or releases impurities under deprotection/cleavage conditions.

(2) What it affects: directly influences crude impurity profiles and downstream processing difficulty.

(3) Example: ChemMatrix descriptions often emphasize that its polyether backbone provides higher stability and reduces leaching risk.

Practical selection logic

1. First decide the desired C-terminus: acid (–COOH) or amide (–CONH₂).

2. Then decide how mild cleavage needs to be: do you need to retain protecting groups / perform fragment condensation (favoring 2-CTC / SASRIN / Sieber, etc.)?

a) Mild/super-acid-labile release (to obtain protected fragments or acid-sensitive targets) → Rink acid (super acid-labile acid) / 2-CTC (low-acid, short-time release) / Sieber (super acid-labile amide)

b) Conventional final-peptide cleavage + global side-chain deprotection → Wang (acid) / Rink Amide (amide) (with TFA cocktail)

3. Consider sequence difficulty (long, hydrophobic, aggregation-prone) → prefer lower loading and a matrix with better swelling/more hydrophilicity (e.g., PEG–PS or PEG-based).

4. Finally check engineering parameters: mesh size, %DVB, swelling volume, whether it is preloaded, etc.

Panorama Selection Guide for SPPS (Solid-Phase Peptide Synthesis) Resins and Supporting Materials: Navigation Table + Fmoc/Boc Resin Lists + Backbone Resins & Reagent Toolbox

SPPS Resin Selection Navigation: decide the route (Fmoc/Boc) → decide the C-terminus (acid/amide) → then choose preloaded vs. mild cleavage

Problem to solve (define the task first)	Which table to check first	How to choose within the table	Typical use scenarios	Key reminders
You are doing Fmoc-SPPS and need a “synthesis resin”	Table 1 | Common Fmoc-SPPS resins	Choose C-terminus type (acid / amide) → then decide if you need preloaded or mild / super-acid-labile cleavage (2-CTC / Sieber) → pick the specific item	Routine lab synthesis, automated synthesis, most customer selections	Deciding the product C-terminus first is the most critical (acid vs amide); otherwise it is hard to fix later
You clearly need a C-terminal acid (–COOH) peptide (Fmoc route)	Table 1 (C-terminal acid section)	Need mild cleavage/fragment strategy → choose 2-CTC; want a fast start → choose Fmoc-AA–Wang preloaded; conventional acid route → choose Rink acid / Wang	Conventional acid peptides, sensitive sequences, fragment condensation	2-CTC is more for “mild/fragment”; preloaded reduces variability in the first-residue loading step
You clearly need a C-terminal amide (–CONH₂) peptide (Fmoc route)	Table 1 (C-terminal amide section)	General purpose → choose Rink Amide (different loading/backbone options) → select by loading level/particle size	Most therapeutic peptides, protein fragments, common functional peptides	Same “Rink amide family” but different loadings: long/hydrophobic peptides often benefit from lower loading
You are doing Boc-SPPS (or continuing a classic Boc process)	Table 3 | Classic Boc-SPPS resins & preloaded resins	For acid terminus → choose Boc-AA–PAM preloaded; for amide terminus → choose BHA / MBHA	Classic Boc route, legacy process continuation	Boc vs Fmoc use different deprotection/cleavage systems; resin choice must match the process chemistry
You want to start fast / reduce error from first-residue loading	Table 1 or Table 3 (preloaded entries)	Fmoc route → Fmoc-AA–Wang resin; Boc route → Boc-AA–PAM resin	Beginners, method development, high batch consistency needs	Preloaded resins reduce starting-step variability, but still must match the target C-terminus
You need mild cleavage or protected fragments / fragment condensation	Table 1 (2-CTC / Sieber)	Acid fragments / mild release → 2-CTC; even milder acid-labile amide / fragments → Sieber Amide	Sensitive modifications, difficult peptides, fragment strategies	If the goal is “mild release/fragments,” prioritize these rather than standard Wang/Rink
You do not want a finished linker resin; you want to install a linker / modify a resin yourself	Table 2 | Backbone / starting functionalized resins	Choose chloromethyl PS (Merrifield/CM-PS) or aminomethyl PS (AM-PS) → then install/derivatize linker	Process development, custom resins, special functionalization needs	Table 2 is a toolbox for “building/modifying resins”; routine synthesis usually starts with Table 1/Table 3

Table 1 | Common Fmoc-SPPS Resins: C-terminal acid (Wang/2-CTC/Rink acid) × C-terminal amide (Rink amide) × super-acid-labile/fragment (Sieber) × preloaded resins

Category	CAS No.	Aladdin Cat. No.	Product name	Specification / Purity	Role (SPPS-related)
Fmoc-SPPS | C-terminal acid | 2-CTC (mild cleavage / fragments)	934816-82-7	C590778	2-Chlorotrityl resin	100–200 mesh, 1% DVB, 0.4–3.0 mmol/g	For Fmoc-SPPS to obtain C-terminal carboxylic acid (–COOH) peptides; enables milder acidic cleavage, suitable for sensitive sequences, protected fragments, and fragment condensation strategies.
Fmoc-SPPS | C-terminal acid | 2-CTC (mild cleavage / fragments)	934816-82-7	C301835	2-Chlorotrityl chloride resin	0.8–1.5 mmol/g, 70–200 mesh, 1% DVB	For Fmoc-SPPS C-terminal acid (–COOH) peptides; commonly used for milder release/fragment strategies to reduce risks associated with harsh acid conditions.
Fmoc-SPPS | Preloaded resin | Wang (C-terminal acid)	_	C116088	Fmoc-Cys(Trt)-Wang resin	100–200 mesh, 1% DVB, substitution 0.3–0.8 mmol/g	Preloaded with the first amino acid (Fmoc-Cys(Trt)) for Fmoc-SPPS C-terminal acid peptides; avoids first-residue loading and improves starting consistency.
Fmoc-SPPS | Preloaded resin | Wang (C-terminal acid)	_	P118257	Fmoc-Phe-Wang resin	100–200 mesh, 1% DVB, substitution 0.3–0.8 mmol/g	Preloaded with the first amino acid (Fmoc-Phe) for Fmoc-SPPS C-terminal acid peptides; enables fast start and better batch-to-batch consistency.
Fmoc-SPPS | C-terminal acid | Rink acid (super-acid-labile / mild release)	_	R466724	Rink acid resin	50–100 mesh, labeled range: 0.6–0.8 mmol/g loading, 1% divinylbenzene crosslinked	For Fmoc-SPPS C-terminal carboxylic acid (–COOH) peptides; provides a linker option and cleavage window different from Wang/2-CTC.
Fmoc-SPPS | C-terminal acid | Rink acid (super-acid-labile / mild release)	_	R466302	Rink acid resin	100–200 mesh, labeled range: 0.5–1.5 mmol/g loading, 1% divinylbenzene crosslinked	For Fmoc-SPPS C-terminal acid (–COOH) peptides; different particle size/loading allows selection by sequence difficulty and filtration/scale-up needs.
Fmoc-SPPS | C-terminal amide | Rink Amide (MBHA type)	431041-83-7	R589109	Rink Amide MBHA resin	100–200 mesh, 1% DVB, 0.3–0.8 mmol/g	For Fmoc-SPPS to obtain C-terminal amide (–CONH₂) peptides (classic general-purpose amide resin).
Fmoc-SPPS | C-terminal amide | Rink Amide (AM type)	183599-10-2	R118279	Rink Amide-AM resin	0.3–0.8 mmol/g, 100–200 mesh, 1% DVB	For Fmoc-SPPS C-terminal amide (–CONH₂) peptides; general-purpose for routine sequences.
Fmoc-SPPS | C-terminal amide | Rink Amide (4-methylbenzhydrylamine, polymer-bound)	_	R118280	Polymer-bound Rink amide 4-methylbenzhydrylamine	0.3–0.8 mmol/g, 100–200 mesh, 1% DVB	For Fmoc-SPPS C-terminal amide peptides; polymer-bound linker suitable for standard solid-phase workflows.
Fmoc-SPPS | C-terminal amide | Rink Amide (4-methylbenzhydrylamine, polymer-bound)	_	R476014	Rink amide 4-methylbenzhydrylamine, polymer-bound	Labeled range: ~1.1 mmol/g loading	For Fmoc-SPPS C-terminal amide peptides; higher loading suits short, non-aggregating sequences or high-yield needs.
Fmoc-SPPS | C-terminal amide | Rink Amide (4-methylbenzhydrylamine, polymer-bound)	_	R476070	Rink amide 4-methylbenzhydrylamine, polymer-bound	Labeled range: ~0.5 mmol/g loading	For Fmoc-SPPS C-terminal amide peptides; lower loading is more favorable for long/hydrophobic peptides to reduce crowding and aggregation.
Fmoc-SPPS | C-terminal amide | Rink Amide (AM-PS backbone)	_	R476017	Rink amide (aminomethyl) polystyrene	Labeled range: ~1.1 mmol/g loading	For Fmoc-SPPS C-terminal amide peptides; amide resin format based on aminomethyl polystyrene.
Fmoc-SPPS | C-terminal amide | Rink amide/amine series	_	R466300	Rink amine resin	100–200 mesh, labeled range: 0.5–1.5 mmol/g N loading, 1% divinylbenzene crosslinked	Rink-series (N-loading) anchoring/release strategy used in solid-phase peptide synthesis; commonly used to obtain C-terminal amide-type products or related amide routes.
Fmoc-SPPS | C-terminal amide | Rink amide series	_	R466726	Rink amide resin	50–90 mesh, labeled range: 0.8–1.0 mmol/g N loading	For Fmoc-SPPS C-terminal amide (–CONH₂) peptides; larger particles facilitate filtration/scale-up handling.
Fmoc-SPPS | Super-acid-labile | Sieber Amide (amide / fragments)	915706-90-0	S118282	Sieber amide resin	0.3–0.8 mmol/g, 100–200 mesh, 1% DVB	Super-acid-labile amide linker: enables milder acidic release of C-terminal amide peptides or protected fragments; useful for fragment condensation and sensitive modification strategies.
Fmoc-SPPS | Super-acid-labile | Sieber Amide (amide / fragments)	915706-90-0	F347706	Sieber amide resin	100–200 mesh, 1% DVB, 0.1–2.8 mmol/g	Super-acid-labile amide linker: broader loading range enables choosing lower loading for difficult sequences to reduce aggregation and improve coupling completeness.

Table 2 | Solid-Phase “Backbone / Starting Functionalized Resins” (for installing linkers or derivatization to prepare various resins)

Category	CAS No.	Aladdin Cat. No.	Product name	Specification / Purity	Role (SPPS-related)
General backbone resin | Chloromethyl (Merrifield / CM-PS)	55844-94-5	M432913	Merrifield peptide resin	200–400 mesh, labeled range: 1.0–1.5 mmol/g Cl loading, 2% crosslinked	Classic chloromethyl polystyrene solid support/backbone; used for SPPS-related derivatization (installing linkers/functional groups) and some classic routes.
General backbone resin | Chloromethyl (Merrifield / CM-PS)	55844-94-5	M432916	Merrifield peptide resin	50–100 mesh, labeled range: 2.5–4.0 mmol/g Cl loading, 1% divinylbenzene crosslinked	Chloromethyl PS backbone; particle size/loading options match different scales, filtration, and diffusion needs.
General backbone resin | Chloromethyl (Merrifield / CM-PS)	55844-94-5	M432914	Merrifield peptide resin	200–400 mesh, labeled range: 2.0–2.5 mmol/g Cl loading, 2% crosslinked	Chloromethyl PS backbone; crosslinking affects swelling/diffusion vs mechanical strength, for resin derivatization and process matching.
General backbone resin | Chloromethyl (Merrifield / CM-PS)	55844-94-5	M432915	Merrifield peptide resin	200–400 mesh, labeled range: 3.5–4.5 mmol/g Cl loading, 1% crosslinked	High-loading chloromethyl PS backbone; suitable when higher loading is desired (while considering steric hindrance/aggregation for long peptides).
General backbone resin | Chloromethyl (CM-PS)	55844-94-5	C110262	Chloromethylated polystyrene resin, 1% DVB crosslinked	1.0–1.24 mmol/g, 100–200 mesh, 1% DVB	Chloromethyl PS functionalized backbone for installing linkers/building various solid supports or related immobilization strategies.
General backbone resin | Chloromethyl (CM-PS)	55844-94-5	C684314	Chloromethyl polystyrene resin	2% DVB crosslinked (100–200 mesh), 0.8–1.2 mmol/g	Chloromethyl PS functionalized backbone; 2% crosslinking improves mechanical strength and alters swelling/diffusion for different conditions/equipment.
General backbone resin | Aminomethyl (AM-PS)	89551-24-6	A348464	Aminomethyl polystyrene resin	200–400 mesh, extent of labeling: 1.5–2.0 mmol/g loading, 2% crosslinked	AM-PS backbone; commonly used to install Rink/Wang linkers or to prepare preloaded resins and other derivatized solid supports.

Table 3 | Classic Boc-SPPS Resins & Preloaded Resins: PAM (acid terminus) × BHA/MBHA (amide terminus)

Category	CAS No.	Aladdin Cat. No.	Product name	Specification / Purity	Role (SPPS-related)
Boc-SPPS | Preloaded resin | Boc-AA–PAM (C-terminal acid)	_	B476081	Boc-Glu(OcHx)-PAM resin	Labeled range: ~0.7 mmol/g loading	Preloaded first Boc amino acid on the PAM system; starting support for Boc-SPPS to obtain C-terminal carboxylic acid (–COOH) peptides.
Boc-SPPS | Preloaded resin | Boc-AA–PAM (C-terminal acid)	_	B476082	Boc-Pro-PAM resin	Labeled range: ~0.7 mmol/g loading	Preloaded Boc-AA on PAM; starting support for Boc-SPPS C-terminal acid peptides, enabling rapid start and batch consistency.
Boc-SPPS | Preloaded resin | Boc-AA–PAM (C-terminal acid)	_	B476074	Boc-Thr(Bzl)-PAM resin	Labeled range: ~0.6 mmol/g loading	Preloaded Boc-AA on PAM; starting solid support for Boc-SPPS C-terminal acid peptides.
Boc-SPPS | Preloaded resin | Boc-AA–PAM (C-terminal acid)	_	B476076	Boc-Trp(For)-PAM resin	Labeled range: ~0.6 mmol/g loading	Preloaded Boc-AA on PAM; for Boc-SPPS C-terminal acid peptides, reducing variability in the initial loading step.
Boc-SPPS | Preloaded resin | Boc-AA–PAM (C-terminal acid)	_	B476071	Boc-β-Ala-PAM resin	Labeled range: ~0.5 mmol/g loading	Preloaded Boc-AA on PAM; a solid-phase starting point for Boc-SPPS C-terminal acid peptides.
Boc-SPPS | C-terminal amide | BHA-PS	_	B466478	BHA–polystyrene	200–400 mesh, labeled range: 0.7–1.4 mmol/g loading, 1% crosslinked	Classic BHA amide resin; for Boc-SPPS to obtain C-terminal amide (–CONH₂) peptides.
Boc-SPPS | C-terminal amide | MBHA-PS	_	M118275	MBHA resin	0.3–0.8 mmol/g, 100–200 mesh, 1% DVB	Classic MBHA amide resin; for Boc-SPPS C-terminal amide peptides.
Boc-SPPS | C-terminal amide | MBHA-PS	_	M466476	MBHA resin	200–400 mesh, labeled range: 0.5–1.0 mmol/g loading, 1% crosslinked	MBHA amide resin (different particle size/loading); for Boc-SPPS C-terminal amide peptides, selectable by filtration/diffusion and yield needs.

Table 4 | Common Supporting Chemicals for SPPS (Solvents / Deprotection / Coupling / Cleavage & Scavengers / Workup)

Category	Chemical name	CAS	Role (SPPS-related)
Solvent	N,N-Dimethylformamide (DMF)	68-12-2	The most commonly used polar solvent for Fmoc-SPPS: swells resin, dissolves amino acids/coupling reagents, used for washing and as reaction medium.
Solvent	Dichloromethane (DCM / Methylene chloride)	75-09-2	Classic solvent for washing/swelling and solvent switching (especially common with PS resins); also used for certain pre-/post-coupling or capping washes.
Solvent	N-Methyl-2-pyrrolidone (NMP)	872-50-4	High-boiling polar solvent, often used as a DMF alternative/supplement; improves swelling and mass transfer/solubility for difficult couplings or fragments.
Solvent (analytical/prep)	Acetonitrile (ACN)	75-05-8	Common organic phase for analytical/preparative HPLC of crude peptides/intermediates; also used for some washing/solvent exchange.
Deprotection (Fmoc)	Piperidine	110-89-4	Standard base for Fmoc deprotection (commonly 10–20% in DMF, etc.); removes N-terminal Fmoc to expose the free amine for the next coupling cycle.
Cleavage / global deprotection (common for Fmoc products)	Trifluoroacetic acid (TFA)	76-05-1	Cleaves peptides from acid-labile linkers/resins and removes most acid-labile side-chain protecting groups (often used with scavengers).
Base / acid scavenger	N,N-Diisopropylethylamine (DIPEA / Hünig’s base)	7087-68-5	Base and “acid scavenger” in coupling: supports carboxyl activation systems, increases amine nucleophilicity, neutralizes acidic byproducts.
Coupling (uronium/phosphonium)	HATU	148893-10-1	High-efficiency coupling reagent for carboxyl activation; often used to improve coupling at difficult sites/fragments.
Coupling (uronium)	HBTU	94790-37-1	Classic general-purpose coupling reagent; activates carboxylic acids to reactive intermediates to drive peptide bond formation.
Coupling (phosphonium)	PyBOP	128625-52-5	Common phosphonium coupling reagent; used in solid-/solution-phase peptide coupling (often as an alternative/complement to HBTU/HATU).
Coupling (carbodiimide)	DIC (N,N′-Diisopropylcarbodiimide)	693-13-0	Common carbodiimide activator; often paired with additives (e.g., Oxyma/HOBt) to improve efficiency and reduce side reactions.
Coupling (carbodiimide)	DCC (N,N′-Dicyclohexylcarbodiimide)	538-75-0	Traditional carbodiimide coupling agent (used in both solid- and solution-phase); activates carboxyl groups to coupling-competent intermediates.
Coupling additive	Oxyma Pure	3849-21-6	Often paired with DIC/DCC: improves coupling efficiency and suppresses some side reactions (including racemization-related risks).
Coupling additive	HOBt (1-Hydroxybenzotriazole)	2592-95-2	Classic additive that promotes activation and suppresses side reactions (note its safety/regulatory considerations).
Capping (optional)	Acetic anhydride	108-24-7	Caps unreacted free amines to reduce impurities arising from deletion-sequence elongation.
Cleavage scavenger	Triisopropylsilane (TIS)	6485-79-6	Common scavenger in TFA cleavage cocktails; captures reactive cations/alkylating species to reduce side reactions.
Cleavage scavenger	Anisole (methoxybenzene)	100-66-3	Common scavenger; helps absorb/capture reactive intermediates and reduce side-chain modification side reactions.
Cleavage scavenger	Thioanisole	100-68-5	Stronger sulfur-directed scavenger; often used in harsher/more sensitive deprotection systems to suppress side reactions.
Cleavage scavenger	1,2-Ethanedithiol (EDT)	540-63-6	Strong thiol scavenger; particularly important for sequences prone to alkylation/rearrangement side reactions (often used with TFA systems).
Workup	Diethyl ether	60-29-7	Common precipitation/washing solvent for crude peptides: precipitates peptides from cleavage liquor to enable solid–liquid separation and removal of organic impurities.
Non-resin supporting material	Poly(ethylene glycol) (PEG; various MW/solutions)	25322-68-3	Used in some processes as a non-resin supporting material (e.g., solvent system aid, viscosity adjustment, process additive).
(Boc route / historical classic) cleavage reagent	Hydrogen fluoride (HF)	7664-39-3	Classic Boc-SPPS reagent for “strong-acid cleavage/global deprotection” (extremely hazardous and tightly regulated; discussed/used only under compliant safety and protection conditions).

Aladdin: https://www.aladdinsci.com/