Crystal‐state structural analysis of two γ‐lactam‐restricted analogs of Pro‐Leu‐Gly‐NH2

G. VALLE, M. CRISMA, C. TONIOLO, K. ‐L YU, R. L. JOHNSON

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Abstract

The crystal structures of two analogs of Pro‐Leu‐Gly‐NH, (1), containing a γ‐lactam conformational constraint in place of the ‐Leu‐Gly‐ sequences, are described. The highly biologically active (S,R)‐diastere‐omer 2a is semi‐extended at the C‐terminus, with the N‐terminal Pro residue in the unusual “C5” conformation [ψ1=– 0.8(15)°] stabilized by a (peptide)N‐H…N(amino) intramolecular H‐bond [the N(3)…N(4) separation is 2.687(11)Å]. Conversely, the N,N′‐isopropylidene aminal trihydrate of the (S,S)‐diastereomer 2b, compound 3, adopts a β‐bend conformation at the C‐terminus, as already reported for 1. However, the backbone torsion angles [φ= 57.4(4), ψ2=– 129.9(3)°; ψ3= ‐ 92.3(4), ψ3= 6.4(5)°] lie close to the values expected for the corner residues of an ideal type‐II β‐bend. A weak intramolecular 4 → 1 H‐bond is seen between the Gly carboxyamide anti‐NH and Pro C=O groups. In the newly formed 2,2,3,4‐tetraalkyl‐5‐oxo‐imidazolidin‐1‐yl moiety the ψ1 torsion angle is 12.9(4)° and the intramolecular N(3)…N(4) separation is 2.321(4)Å.

Original languageEnglish (US)
Pages (from-to)181-190
Number of pages10
JournalInternational Journal of Peptide and Protein Research
Volume33
Issue number3
DOIs
StatePublished - Mar 1989

Keywords

  • Pro‐Leu‐Gly‐NH
  • conformational constraints
  • crystal structures
  • imidazolidinone derivative
  • lactam analogs

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