TY - JOUR
T1 - Examination of the conformational meaning of "δ-address" in the dermenkephalin sequence
AU - Nikiforovich, Gregory V.
AU - Hruby, Victor J.
N1 - Funding Information:
We are grateful to Dr. Andrzej W. Lipkowski and to Ms. Silvia Cavagnero for drawing our attention to some of the above problems and for helpful discussions and consultations. This work was supported by U. S. Public Service Grants DA 06284 and NS 19972.
PY - 1990/12/14
Y1 - 1990/12/14
N2 - Comprehensive energy calculations were applied to four opioid-related peptides with different receptor selectivities, namely the δ-selective dermenkephalin (Tyr-D-Met-Phe-His-Leu-Met-Asp-NH2, DRE), the μ-selective dermorphin (Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2, DRM) and their "hybrid" peptides DRM/DRE (Tyr-D-Ala-Phe-Gly-Leu-Met-Asp-NH2) and DRE/DRM (Tyr-D-Met-Phe-His-Tyr-Pro-Ser-NH2). It was shown that the N-terminal tripeptide "μ-messages" in the δ-selective ligands DRE and DRM/DRE can possess similar low energy space arrangements of their functionally important elements (the N-terminal α-amino group and the aromatic moieties of Tyr and Phe), but that these are different from the space arrangement of these moieties in μ-selective DRM and DRE/DRM. These results suggest that the C-terminal tripeptide "δ-address" in DRE may influence the conformation of the "μ-message" in DRM. A refined model for the δ-receptor-bound conformation of DRE is proposed based on these calculations which is similar to that previously suggested for the cyclic δ-selective peptide [D-Pen2, D-Pen5]enkephalin (DPDPE). This model also has partial correspondence with the structure of the δ-selective alkaloid naltrindole.
AB - Comprehensive energy calculations were applied to four opioid-related peptides with different receptor selectivities, namely the δ-selective dermenkephalin (Tyr-D-Met-Phe-His-Leu-Met-Asp-NH2, DRE), the μ-selective dermorphin (Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2, DRM) and their "hybrid" peptides DRM/DRE (Tyr-D-Ala-Phe-Gly-Leu-Met-Asp-NH2) and DRE/DRM (Tyr-D-Met-Phe-His-Tyr-Pro-Ser-NH2). It was shown that the N-terminal tripeptide "μ-messages" in the δ-selective ligands DRE and DRM/DRE can possess similar low energy space arrangements of their functionally important elements (the N-terminal α-amino group and the aromatic moieties of Tyr and Phe), but that these are different from the space arrangement of these moieties in μ-selective DRM and DRE/DRM. These results suggest that the C-terminal tripeptide "δ-address" in DRE may influence the conformation of the "μ-message" in DRM. A refined model for the δ-receptor-bound conformation of DRE is proposed based on these calculations which is similar to that previously suggested for the cyclic δ-selective peptide [D-Pen2, D-Pen5]enkephalin (DPDPE). This model also has partial correspondence with the structure of the δ-selective alkaloid naltrindole.
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U2 - 10.1016/S0006-291X(05)80065-8
DO - 10.1016/S0006-291X(05)80065-8
M3 - Article
C2 - 1979733
AN - SCOPUS:0025603019
SN - 0006-291X
VL - 173
SP - 521
EP - 527
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -