(alphaMe)Nva: stereoselective syntheses and preferred conformations of selected model peptides.
Using different stereoselective chemical and chemoenzymatic approaches we synthesized the chiral, Calpha-methylated alpha-amino acid L-(alphaMe)Nva with a short, linear side-chain. A set of terminally protected model peptides to the pentamer level containing either (alphaMe)Nva or Nva in combination with Ala and/or Aib was prepared using solution methods and characterized fully. Two (alphaMe)Nva peptides were also synthesized using side-chain hydrogenation of the corresponding Calpha-methyl, Calpha-allylglycine (Mag) peptides. A detailed solution and crystal-state conformational analysis based on FT-IR absorption, 1H NMR and X-ray diffraction techniques allowed us to define that: (i) (alphaMe)Nva is an effective beta-turn and 3(10)-helix former; and (ii) the relationship between (alphaMe)Nva chirality and the screw sense of the turn/helix formed is that typical of protein amino acids, i.e. L-(alphaMe)Nva induces the preferential formation of right-handed folded structures. In more general terms, this study reinforced previous conclusions that peptides based on alpha-amino acids with a Calpha-methyl substituent and a Calpha-linear alkyl substituent are characterized by a strong tendency to fold into turn and helical structures.
Moretto
A
A
Biopolymer Research Center, CNR, Department of Organic Chemistry, University of Padova, Italy.
Peggion
C
C
Formaggio
F
F
Crisma
M
M
Toniolo
C
C
Piazza
C
C
Kaptein
B
B
Broxterman
Q B
QB
Ruiz
I
I
Díaz-de-Villegas
M D
MD
Galvez
J A
JA
Cativiela
C
C
D003460:Crystallization; D003497:Cyclic N-Oxides; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012996:Solutions; D017550:Spectroscopy, Fourier Transform Infrared; D013237:Stereoisomerism; D014633:Valine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D014961:X-Ray Diffraction
D003497:Cyclic N-Oxides; D009842:Oligopeptides; D012996:Solutions; C104340:2-methylnorvaline; D014633:Valine; C003959:TEMPO