Peptide design guidelines

The composition in amino acid of a peptide can have various impacts regarding its synthesis or its solubility. Here are few basic things you have to know when designing a peptide:

• Avoid peptide with more than 50% hydrophobic amino acids content (see section “peptide solubility“). Mutate by polar aa such as Gly or Pro
• Try to have charged residues in the sequence (R, K, D, E)
• Basic peptides have to be preferred (positive net charge)
• Avoid Q (Gln) in N-terminal extremity, it tends to cyclize during the chemical production
• Avoid -DG- sequences
• Shorter is better. Short sequences <20 amino acids are more easy to synthesize
• Avoid oxidation-sensitive amino acids (Met, Cys, Trp). Met can eventually be replaced by Noreleucin, cystein by serine, tryptophane by lysine
• Highly acid peptides can be capped in N-ter by acetyl group to gain a negative charge
• Highly basic peptide can be amidated in C-ter to gain a positive charge