Collect. Czech. Chem. Commun. 1988, 53, 2863-2876

Synthesis and X-ray diffraction analysis of the tetrazole peptide analogue Pro-LeuΨ[CN4]Gly-NH2

Giovanni Vallea, Marco Crismaa, Kuo-Long Yub, Claudio Tonioloa, Ram K. Mishrac and Rodney L. Johnsonb

a Biopolymer Research Centre, C. N. R., Department of Organic Chemistry, University of Padova, 35131 Padova, Italy
b Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, 55455 U.S.A.
c Departments of Psychiatry and Neurosciences, McMaster University, Health Sciences Center, Hamilton, Ontario, Canada, L8N 3Z5


The synthesis of an analogue of the neuropharmacologically active peptide Pro-Leu-Gly-NH2 in which the Leu-Gly peptide bond has been replaced with a tetrazole moiety was carried out. The molecular and crystal structure of the tetrazole analogue Pro-Leuψ[CN4]Gly-NH2 was determined by X-ray diffraction and a comparison was made with the published X-ray structure of Pro-Leu-Gly-NH2. The tetrazole annular system turns out to be a good conformationally-restricted replacement for the cis-peptide bond in terms of bond lengths, bond angles and the ω torsion angle. The molecule was found to be folded at the -Leuψ[CN4]Gly- sequence, but it did not form the intramolecular N-H···O=C hydrogen bond characteristic of the type Vla β-bend conformation. In contrast to Pro-Leu-Gly-NH2, Pro-Leuψ[CN4]Gly-NH2 was found to be unable to enhance the binding of dopamine receptor agonists to the dopamine receptor.