Hybrid peptides: expanding the beta turn in peptide hairpins by the insertion of beta-, gamma-, and delta-residues.
The beta turn segment in designed peptide hairpins has been expanded by the insertion of beta-, gamma- and delta-amino acids at the i+2 position. The model octapeptides Boc-Leu-Phe-Val-DPro-Ac6c-Leu-Phe-Val-OMe (1), Boc-Leu-Phe-Val-DPro-beta3-Ac6c-Leu-Phe-Val-OMe (2), and Boc-Leu-Phe-Val-DPro-Gpn-Leu-Phe-Val-OMe (3) have been shown to adopt beta hairpin conformations in methanol by the observation of key diagnostic nuclear Overhauser effects. Boc-Leu-Val-Val-DPro-delta-Ava-Leu-Val-Val-OMe (4) adopts a beta hairpin conformation in crystals; this is stabilized by three cross-strand hydrogen bonds as demonstrated by X-ray diffraction. The canonical C10 turn in an alpha-alpha segment is expanded to C11, C12, and C13 turns in alpha-beta, alpha-gamma, and alpha-delta segments, respectively. The crystal structures of Piv-LPro-beta3-Ac6c-NHMe (5) and Boc-Ac6c-Gpn-Ac6c-OMe (6) reveal intramolecularly hydrogen-bonded C11 and C12 conformations, respectively. Computer modeling of octapeptide sequences that contain centrally positioned hybrid-turn segments, by using turn parameters derived from the structures of peptides 5 and 6, establishes the stereochemical acceptability of the beta hairpins in the cases of peptides 2 and 3. Accommodation of omega-amino acids into the turn segments is achieved by the adoption of gauche conformations around the backbone C--C bonds.
Rai
Rajkishor
R
Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India.
Vasudev
Prema G
PG
Ananda
Kuppanna
K
Raghothama
Srinivasarao
S
Shamala
Narayanaswamy
N
Karle
Isabella L
IL
Balaram
Padmanabhan
P
D000596:Amino Acids / Q000737:chemistry*; D018360:Crystallography, X-Ray; D008954:Models, Biological; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary
D000596:Amino Acids; D010455:Peptides