Reconstitution is usually described as a procedure. It is better understood as a prediction you can make before you start, because almost everything that determines whether a peptide goes into solution is already written in its sequence. Two calculated numbers carry most of it.
This post works out both for every compound in this catalogue that has a published sequence, and then says what each result means at the bench.
The two numbers
Net charge at pH 7. Arginine and lysine side chains are protonated at neutral pH and carry a positive charge. Aspartate and glutamate are deprotonated and carry a negative one. Histidine sits near its own transition and contributes a fraction. The chain's two ends carry opposite unit charges and cancel. Add it up and you have the molecule's net charge in a neutral aqueous solvent.
Charge is what dissolves a peptide. Like charges repel, so a molecule with a clear net charge is held away from its neighbours and surrounded by water. A molecule whose charges cancel has nothing keeping it apart from the next one, and peptides in that state are the ones that clump, gel or refuse to leave the stopper. The pH at which the charges exactly cancel is the isoelectric point, and it is reliably the pH of worst solubility.
Mean hydropathy. Kyte and Doolittle assigned each amino acid a hydropathy value from +4.5 for isoleucine down to −4.5 for arginine. Averaged over a chain it gives a single figure: positive means the composition is net water-repelling, negative means net water-attracting. It does not predict a concentration. It predicts which direction the molecule leans.
Every sequence in this catalogue, scored
| Compound | Residues | Net charge at pH 7 | Mean hydropathy | Reading |
|---|---|---|---|---|
| Selank | 7 | +2.0 | −2.04 | Strongly basic, strongly hydrophilic |
| GHK-Cu | 3 | +1.1 | −2.50 | Basic, hydrophilic |
| PT-141 | core motif | +1.1 | −1.45 | Basic, hydrophilic |
| Melanotan-2 | core motif | +1.1 | −1.45 | Basic, hydrophilic |
| KPV | 3 | +1.0 | −0.43 | Basic, mildly hydrophilic |
| Semax | 7 | −0.9 | −0.80 | Nearly balanced, mildly hydrophilic |
| Vesugen | 3 | −1.0 | −3.63 | Acidic, very hydrophilic |
| Pinealon | 3 | −1.0 | −3.83 | Acidic, very hydrophilic |
| Prostamax | 4 | −1.0 | −3.12 | Acidic, very hydrophilic |
| Testagen | 4 | −1.0 | −2.83 | Acidic, very hydrophilic |
| SNAP-8 | 8 | −1.0 | −2.41 | Acidic, very hydrophilic |
| Glutathione | 3 | −1.1 | −0.47 | Acidic, mildly hydrophilic |
| Epithalon | 4 | −2.0 | −1.40 | Strongly acidic, hydrophilic |
| BPC-157 | 15 | −2.0 | −0.69 | Strongly acidic, mildly hydrophilic |
| DSIP | 9 | −2.0 | −0.70 | Strongly acidic, mildly hydrophilic |
Three things fall out of that table.
Every compound is hydrophilic. All fifteen mean-hydropathy figures are negative. Not one is in positive territory. That is worth stating plainly because it is why a plain neutral aqueous diluent is the standing default on this catalogue rather than a compromise: nothing here is composed in a way that fights water. It is a fact about what short synthetic research peptides tend to be, built largely from charged and polar residues, and not a general claim about peptides, many of which are strongly hydrophobic and need a cosolvent.
Most compounds have a real net charge. Eleven of the fifteen are at or beyond one full charge unit, and four are at two. Those are the easy ones. Charge does the work and water does the rest, which is the condition the reconstitution solution is formulated for.
One compound sits near balance. Semax computes to about −0.9 with one acidic residue and a histidine, and it is the catalogue's closest approach to charge cancellation. That is not a prediction that semax is hard to dissolve, and in practice it is not; it is the entry in this table whose solubility is most sensitive to the pH it meets. The buffer and pH post covers why that sensitivity exists.
The rule the table encodes
The classical bench heuristic, which the numbers above restate, runs in three steps.
- Count the charges. If the chain is clearly basic, net positive, a mildly acidic aqueous solvent keeps it that way. If it is clearly acidic, net negative, a mildly basic one does. Either way you are pushing further from the isoelectric point, not closer.
- Check the balance. If the positive and negative counts are close, the molecule has an isoelectric point somewhere near neutral and a neutral diluent is the worst available choice. Move away from neutral in whichever direction the chain's majority residue favours.
- Only then consider a cosolvent. A chain with positive mean hydropathy, which nothing in the table above has, is the case for an organic cosolvent. Reaching for one on a hydrophilic peptide adds a variable to the experiment and solves nothing.
Note what step three is not. A cosolvent is a last resort for a composition that water genuinely cannot carry, and for the compounds on this catalogue that condition does not arise. Where a cosolvent does belong is in cell-culture work for reasons other than solubility, which the DMSO post covers separately.
Why the sequence cannot be the whole answer
Composition predicts the direction. It does not predict the number, for three reasons.
Sequence order matters, not only content. Hydropathy averaged over a chain treats the residues as a bag. A real molecule has them in an order, and a run of hydrophobic residues together behaves differently from the same residues scattered, because consecutive ones can form the stretch of beta sheet that nucleates aggregation. The aggregation post goes into that mechanism, and it is the reason a peptide can be hydrophilic on paper and still come out of solution over hours.
Modified ends change the charge. SNAP-8 scores −1.0 in the table from its side chains, but its N-terminus is acetylated and its C-terminus is an amide, which removes both terminal charges rather than letting them cancel. The arithmetic lands in the same place here; on a different sequence it would not. The molecular weight post shows how to spot end modifications from the formula.
Metal complexes are not peptides. GHK-Cu is scored above as the tripeptide, which is what the sequence gives you. The actual molecule carries a copper atom and the peptide's charge state is part of how that copper is held, so the figure in the table describes the ligand and not the complex.
What slow dissolution is and is not
A peptide that takes several minutes to clear is not a peptide that has failed. Lyophilized material has a very high surface area and wets quickly, but a cake can trap air, and the first appearance after adding solvent is often a cloudy suspension that becomes clear on standing. Swirling rather than shaking matters here: shaking drives air into the solution and the air-water interface is where peptides denature and aggregate, which is covered in the post on why peptides stick to plastic.
Acylated compounds are the honest exception to "it should be quick". A fatty-acid chain attached to extend circulating half-life is, by design, a hydrophobic addition to a hydrophilic molecule, and those compounds genuinely take longer. That is the subject of why GLP-1 peptides dissolve slowly, and it is expected behaviour rather than a defect.
What is not normal is material that stays visibly particulate after standing, a solution that turns from clear to cloudy later, or a gel. Those are aggregation, and the useful response is to record it and read the solution-lifetime post, not to apply more force.
Frequently asked questions
Which single number matters more, charge or hydropathy?
Charge, for the peptides in this catalogue. Every one of them is hydrophilic, so hydropathy is not the limiting factor and the charge state is what distinguishes an easy reconstitution from a sensitive one. On a hydrophobic chain the priority reverses.
What is an isoelectric point and why does it matter here?
It is the pH at which the molecule's positive and negative charges exactly cancel, leaving it with no net charge and nothing to keep its molecules apart. Solubility is at its minimum there. The practical use of the number is to know which pH to avoid.
My peptide looks cloudy right after I add solvent. Is that aggregation?
Usually not. A lyophilized cake traps air and the first minute often looks cloudy before clearing on standing. Cloudiness that persists after standing, or that appears later in a solution that was clear, is the one to take seriously.
Does a higher charge mean a peptide is more stable?
No. Charge predicts whether it will dissolve, not whether it will last. Those are different properties with different causes, and stability is read off the residues rather than the charge total, which the post on which residues degrade first sets out.
Can I calculate these numbers for a compound you do not list?
Yes. Count the arginines and lysines as plus one each, the aspartates and glutamates as minus one each, ignore the termini because they cancel, and average the Kyte-Doolittle values over the chain. The citation at the foot of this post has the value table.
Why does this catalogue use one diluent for almost everything?
Because every compound here with a published sequence is hydrophilic and most carry a real net charge, so one neutral aqueous diluent genuinely suits them. The diluent post covers the cases where that default is the wrong call.
References
- Kyte J, Doolittle RF. A simple method for displaying the hydropathic character of a protein. Journal of Molecular Biology 1982;157(1):105-132. The hydropathy values used for every score in this post. doi.org/10.1016/0022-2836(82)90515-0
- Pepstral compound reference data and compound guides: the sequences scored here are the ones published on this site's own compound pages, listed with their molecular formulas in the reference table. Scored 5 October 2026. pepstral.com/research-peptide-reference-table.html
- Powell MF, Nguyen T, Baloian L. Compendium of excipients for parenteral formulations. PDA Journal of Pharmaceutical Science and Technology 1998;52(5):238-311. pubmed.ncbi.nlm.nih.gov/10075506
- Manning MC, Chou DK, Murphy BM, Payne RW, Katayama DS. Stability of protein pharmaceuticals: an update. Pharmaceutical Research 2010;27(4):544-575. doi.org/10.1007/s11095-009-0045-6
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