Hello
I am just wondering if peptide analogues containing D amino acids are more hydrophilic than its L-amino acid-containing analogues in HPLC? I synthesized and folded an all L-peptide, and the HPLC showed two peaks that have the same mass in MS. My possible suspect is the hydroxyproline in my all L-peptide since it is prone to isomerization in these kinds of reactions.
Hoping for your insightful thoughts.
Thank you very much.
No, there is no trend/correlation for D amino acids and hydrophobicity that I'm aware of. Generally, polypeptides can be a bit more tricky compared to typical small molecules because they can adopt various secondary structures which can drastically alter hydrophobicity in unpredictable ways, they don't necessarily correlate to D/L stereochemical configuration. Rotamers are another possibility and there's even precedent for isolable rotamers, surprisingly enough. You are correct in thinking of epimerization first, as this is usually the most frequently encountered problem with peptides, especially with certain synthetic methods.
Full D-isomers and full L-isomers, being enantiomers, should not differ in the interaction with non-chiral agents, so their hydrophilicity (i.e., interaction with water) has to be the same. The situation with mixed D/L peptides is fundamentally different though - since we are dealing now with diastereomers, many of their properties are not identical to each other.
The previous answer from Grant provides a good example of anticipated difference in the secondary structure, which would certainly affect the peptide hydrophilic character.
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