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Thermodynamics of phosphotyrosine peptide–peptoid hybrids binding to the p56 lck SH2 domain
Author(s) -
Dekker F. J.,
DE Mol N. J.,
Liskamp R. M. J.
Publication year - 2010
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.1242
Subject(s) - peptoid , chemistry , peptide , hydrogen bond , amide , peptide bond , stereochemistry , enthalpy , sh2 domain , proto oncogene tyrosine protein kinase src , biochemistry , receptor , organic chemistry , molecule , thermodynamics , physics
Abstract A frequently used approach to transform peptides into more drug‐like compounds is preparation of the corresponding peptoids or peptide–peptoid hybrids. Although peptoids have advantages, there may also be some disadvantages such as their increased flexibility and the reduced ability for hydrogen bond formation due to alkylation of the backbone amide nitrogen, which might affect the free Gibbs energy (Δ G ). To obtain more insight into these contributions to Δ G , we performed thermodynamic analyses on the interaction between peptide–peptoid hybrids, based on the sequence ‐pTyr‐Glu‐Glu‐Ile‐, and the p56 lck (Lck) Src homology 2 domain. van't Hoff analysis was performed on binding data obtained from surface plasmon resonance competition experiments in a temperature range of 10–40 °C. It is observed that amino acid–peptoid substitutions do not have a systemic negative effect on the entropic contributions to Δ G . However, loss in hydrogen‐bonding capacity of the backbone may strongly reduce the binding enthalpy and contribute to the observed lower binding affinity. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.