Nonstereogenic alpha-aminoisobutyryl-glycyl dipeptidyl unit nucleates type I' beta-turn in linear peptides in aqueous solution.
The use of alpha,alpha-disubstituted amino acids represents a valuable strategy to exercise conformational control in peptides. Incorporation of the nonstereogenic alpha-aminoisobutyryl-glycyl (Aib-Gly) dipeptidyl sequence into i+1 and i+2 positions of an acyclic peptide sequence, originally designed and investigated by Gellman and coworkers, [H-Arg-Tyr-Val-Glu-Val-Yyy-Xxx-Orn-Lys-Ile-Leu-Gln-NH2] nucleates a stable [2:4] left-handed type I' beta-turn in water. NMR spectra show that this newly designed beta-hairpin does not aggregate in water up to a concentration of approximately 1 mM, and that its backbone conformation is superimposable on corresponding hairpins containing the DPro-Gly (literature) and Aib-DAla (this work) sequences. The Aib-Gly turn-inducer sequence eliminates complications because of cis-trans isomerization of Zzz-Pro bonds, and constitutes an attractive alternative to the proteogenic Asn-Gly and nonproteogenic DPro-Gly motifs previously suggested as turn-inducer sequences. These design principles could be exploited to prepare water-soluble beta-hairpin peptides with robust structures and novel function.
Masterson
Larry R
LR
Department of Chemistry, University of Minnesota, 207 Pleasant Street SE, Minneapolis, MN 55455, USA.
Etienne
Marcus A
MA
Porcelli
Fernando
F
Barany
George
G
Hammer
Robert P
RP
Veglia
Gianluigi
G
D000577:Amides / Q000737:chemistry; D000621:Aminoisobutyric Acids / Q000737:chemistry*; D002942:Circular Dichroism; D005998:Glycine / Q000737:chemistry*; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry*; D011522:Protons; D012996:Solutions; D013237:Stereoisomerism; D013696:Temperature
D000577:Amides; D000621:Aminoisobutyric Acids; D010455:Peptides; D011522:Protons; D012996:Solutions; C100049:2-aminoisobutyric acid; D005998:Glycine