Conformations and conformational interconversions of diastereomeric cyclic tetraprolines.
Cyclic tetrapeptides exclusively composed of L- and D-Pro have been studied by theoretical means (conformational searches and molecular mechanics calculations using the CHARMM program) supported by 1H-NMR spectroscopy, X-ray analysis and chiroptical measurements. We explored the entire conformational space of the diastereomers cyclo(LLLL-Pro4) (I), cyclo(LDLD-Pro4) (II) and cyclo(LLDD-Pro4) (III) including the low-energy conformations and the related interconversion paths. The conformational interconversions were found to be restricted to cis/trans isomerisations of the amide bonds. Owing to the polycyclic nature of cyclo(Pro4) most of the cis/trans transitions are hindered by energy barriers higher than 30 kcal/mol (up to 150-200 kcal/mol). A few transitions are characterized by computed energy barriers comparable to those found in linear -Xxx-Pro- sequences (approximately 18 kcal/mol), and are therefore experimentally significant. Experimental evidence has been obtained in the case of cyclo(LDLD-Pro4), where two enantiomers are interconverted by a series of 4 cis/trans isomerisations ctct-->cttt-->tttt-->tctt-->tctc. The Erying activation parameters of this reaction were determined in H2O and in DMF by chiroptical measurements (delta H not equal to = 44 and 28 kcal/mol; delta S not equal to = 59 and 22 cal K-1 mol-1, respectively), and correlated with the calculated barriers. In I and III comparable series of four cis/trans isomerisations relate two main conformations with the peptide bond sequences ctct and tctc. In compound I pseudorotational images are interconverted via ctct-->ccct-->cctt-->cctc-->tctc.(ABSTRACT TRUNCATED AT 250 WORDS)
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Department of Theoretical Chemistry, Ulm University, Germany.
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Rothe
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D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000737:chemistry*; D011392:Proline / Q000737:chemistry*; D011487:Protein Conformation; D012984:Software; D013237:Stereoisomerism; D013816:Thermodynamics
D009842:Oligopeptides; D010456:Peptides, Cyclic; D011392:Proline