Design of short linear peptides that show hydrogen bonding constraints in water.
Using a combination of an aromatic amino acid, a homoserine side chain, and a d-amino acid, a series of linear tetrapeptides were designed that adopt an "Hse turn" in water. The conformation was stabilized by intramolecular hydrogen bonds even in the presence of surrounding water molecules. In particular, the peptide with sequence H-Abz-Homoser-Ser-d-Gln-NH(2) showed significant through-space interactions and its free energy of folding is estimated to be on the order of -4 kcal/mol. We report the design of the tetrapeptides using a novel mimicry approach and their characterization based on NMR spectroscopy and MD simulations.
Song
Benben
B
Center for Advanced Drug Research (CADRE), SRI International, Harrisonburg, Virginia 22802, USA.
Kibler
Patrick
P
Malde
Alpeshkumar
A
Kodukula
Krishna
K
Galande
Amit K
AK
D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism; D014867:Water / Q000737:chemistry*
D010455:Peptides; D014867:Water