Structural features of the Pip/AzPip couple in the crystalline state: influence of the relative AzPip location in an azadipeptide sequence upon the induced chirality and conformational characteristics.
Azapipecolic (AzPip) is a pipecolic (Pip) residue analogue containing a nitrogen atom in place of the C(alpha)H group. AzPip was introduced into two reverse dipeptide sequences, Piv-AzPip-L-Ala-NHiPr I and Boc-L-Ala-AzPip-NHiPr II in order to evaluate, in the crystalline state, the influence of the L-Ala-induced chirality upon the prochiral AzPip residue, and therefore the resulting conformational characteristics, according to the relative position of the AzPip residue. Piv-DL-Pip-NHMe III served as a control derivative for comparison between the properties of the two different heterocycles of Pip and AzPip residues. Piperidine and hexahydropyridazine rings have a few characteristics in common: chair conformation, axial disposition of the C-terminal backbone substituent and the cisoid form of the N-terminal tertiary amide function. An almost pure sp3 hybridization state is observed for the substituted nitrogen atom N(alpha), so that L-Ala induces an AzPip (R) or (S) chirality when it follows or precedes, respectively, the azaresidue in such a pseudodipeptide sequence. If both I and II compounds present a short NH...N contact between the sp2 tertiary amide nitrogen atom and the NH of the next secondary amide function, whatever the chiral nature of the sequence, the heterochiral azadipeptide I adopts a rather totally extended conformation while the homochiral azadipeptide II is folded by a beta-VI turn-like structure stabilized by a classical 4-->1 intramolecular hydrogen bond.
Didierjean
C
C
Université Henri Poincaré, Vandoeuvre lès Nancy, France.
Aubry
A
A
Wyckaert
F
F
Boussard
G
G
D001372:Aza Compounds / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004151:Dipeptides / Q000737:chemistry*; D008958:Models, Molecular; D010875:Pipecolic Acids / Q000737:chemistry*; D011487:Protein Conformation; D013237:Stereoisomerism
D001372:Aza Compounds; D004151:Dipeptides; D010875:Pipecolic Acids