ABSTRACT
Azaproline (AzPro) is an analogue of proline containing a nitrogen atom in place of the C(alpha)H group. AzPro has been introduced in various model peptides, and especially in the Boc-Ala-AzPro-Ala-NHiPr tripeptide. The structural consequence of that modification has been investigated in solution by using IR and 1H NMR, with reference to the cognate proline-containing peptide. Contrary to proline, which induces beta-folding of the Pro-Ala sequence, azaproline apparently favors betaVI-folding of the Ala-AzPro one with high occurrence. Opening of the AzPro pyrazolidine ring to get N-methylazaalanine fundamentally does not change the structural properties of the azatripeptide, but allows the existence of open conformers to an extent depending on the solvent.
Subject(s)
Aza Compounds/chemistry , Peptides/chemistry , Proline/analogs & derivatives , Protein Structure, Secondary , Dimethyl Sulfoxide/pharmacology , Magnetic Resonance Spectroscopy , Models, Molecular , Molecular Conformation , Molecular Structure , Protein Folding , StereoisomerismABSTRACT
To determine the structural perturbations induced by the C alpha H-->N alpha exchange in aza-peptides, we have examined by 1H NMR and IR spectroscopy various derivatives of the aza-analogues of alanine, aspartic acid and asparagine in different organic solvents with increasing polarity. Their general formulas are: R1-AzXaa-NR2R3, R1-Pro-AzXaa-NR2R3 and R1-AzXaa-Pro-NR2R3 (where AzXaa denotes the aza-analogue of the amino acid residue Xaa = Ala, Asp, Asn; R1 = Boc, Z; R2, R3 = H, Me, iPr). The aza-analogue of an amino acid residue appears to be a strong beta-turn-inducing motif, and the AzAsn carboxamide side-chain is capable of interacting, as a proton donor, with the preceding peptide carbonyl group.
Subject(s)
Alanine/chemistry , Asparagine/chemistry , Aza Compounds/chemistry , Peptides/chemistry , Models, Molecular , Molecular Structure , Protein ConformationABSTRACT
Reduced dipeptides with the general formula RCO-Xaa-rXbb-N+HR'R" (rXbb, reduced analogue of residue Xbb: NH-C alpha HR1-CrH2) are shown to adopt a folded conformation in solution and in the solid state. The protonated reduced amide bond is an active proton donor capable of interacting with a peptide carbonyl to give a strong hydrogen bond topologically equivalent to the i+2 or i+3-->i interaction. The resulting conformation is similar to the y- or beta-turn structure found in peptides and proteins.
Subject(s)
Dipeptides/chemistry , Protein Folding , Protons , Crystallization , Dipeptides/chemical synthesis , Dipeptides/metabolism , Models, Chemical , Oxidation-Reduction , Protein Conformation , X-Ray DiffractionABSTRACT
The folded structure induced by the N-aminoproline residue (the hydrazino analogue of proline, denoted hPro) in the Boc-Gly1-hPro2-Gly3-NHiPr hydrazino tripeptide has been characterized in the solid state by X-ray diffraction, and compared to the usual beta II-turn structure in the Boc-Gly1-Pro2-Gly36-NHiPr cognate tripeptide. It is stabilized by a bifurcated hydrogen bond in which (Gly3)NH interacts with both (Gly1)CO and (hPro2)N alpha. This conformation is retained in CH2Cl2 and CHCl3 solutions, and allows an overall folded conformation of the hydrazino tripeptide in which (iPr)NH is hydrogen-bonded to (Boc)CO. The hPro alpha-hydrazino acid residue appears to promote a local folded structure, and might behave as a beta-turn mimic.
