Designed beta-hairpin peptides with defined tight turn stereochemistry.
The conformational analysis of two synthetic octapeptides, Boc-Leu-Val-Val-D-Pro-L-Ala-Leu-Val-Val-OMe (1) and Boc-Leu-Val-Val-D-Pro-D-Ala-Leu-Val-Val-OMe (2) has been carried out in order to investigate the effect of beta-turn stereochemistry on designed beta-hairpin structures. Five hundred megahertz (1)H NMR studies establish that both peptides 1 and 2 adopt predominantly beta-hairpin conformations in methanol solution. Specific nuclear Overhauser effects provide evidence for a type II' beta-turn conformation for the D-Pro-L-Ala segment in 1, while the NMR data suggest that the type I' D-Pro-D-Ala beta-turn conformation predominates in peptide 2. Evidence for a minor conformation in peptide 2, in slow exchange on the NMR time scale, is also presented. Interstrand registry is demonstrated in both peptides 1 and 2. The crystal structure of 1 reveals two independent molecules in the crystallographic asymmetric unit, both of which adopt beta-hairpin conformations nucleated by D-Pro-L-Ala type II' beta-turns and are stabilized by three cross-strand hydrogen bonds. CD spectra for peptides 1 and 2 show marked differences, presumably as a consequence of the superposition of spectral bands arising from both beta-turn and beta-strand conformations.
Das
C
C
Molecular Biophysics Unit, Indian Institute of Science, Bangalore-560 012, India.
Naganagowda
G A
GA
Karle
I L
IL
Balaram
P
P
D002942:Circular Dichroism; D003460:Crystallization; D018360:Crystallography, X-Ray; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D015202:Protein Engineering; D017433:Protein Structure, Secondary
D010455:Peptides