D-Ala2]-Deltorphin I peptoid and retropeptoid analogues: synthesis, biological activity and conformational investigations. |
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Authors: | Laura Biondi Elisa Giannini Fernando Filira Marina Gobbo Lucia Negri Raniero Rocchi |
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Institution: | Department of Organic Chemistry, University of Padova, Institute of Biomolecular Chemistry, CNR, Section of Padova, via Marzolo, 1, 35131 Padova, Italy. |
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Abstract: | The synthesis is described of a D-Ala2]-deltorphin I peptoid analogue in which all amino acid residues have been substituted by the corresponding N-alkylglycine residues. The D-Ala2]-deltorphin I retropeptoid was also prepared as well as Ala1 ,D-Ala2]-deltorphin 1 and the corresponding peptoid. Structural investigations by FT-IR and fluorescence measurements were carried out on the synthetic analogues and on some D-Ala2]-deltorphin 1 peptide-peptoid hybrids previously prepared. According to the fluorescence measurements the distance between the aromatic residues in the deltorphin I peptoid and retropeptoid is similar to that suggested for the delta- and micro-opioids, respectively. Measurements of CD in the presence of beta-cyclodextrin, and some preliminary pharmacological experiments were also performed. No dichroic bands are present in the spectrum of the Ntyr1,D-Ala2]-deltorphin I, but an increasing dichroic effect appears in the spectra of both the deltorphin I peptoid and retropeptoid. Activity tests on isolated organ preparations showed that the modifications made produced a dramatic decrease in the agonistic activity of the synthetic derivatives. |
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Keywords: | biological activity conformation deltorphin opioid peptides peptide synthesis peptoids retropeptoids |
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