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001-es BibID:	BIBFORM063962
Első szerző:	Borics Attila
Cím:	The Effect of Pro2 Modifications on the Structural and Pharmacological Properties of Endomorphin-2 / Attila Borics, Jayapal R. Mallareddy, István Timári, Katalin E. Kövér, Attila Keresztes, Géza Tóth
Dátum:	2012
ISSN:	0022-2623 1520-4804
Megjegyzések:	Endomorphins (EM-1 and EM-2) are selective, high affinity agonists of the ?-opioid (MOP) receptor, an important target in pain regulation. Their clinical use is impeded by their poor metabolic stability and limited entry to the central nervous system. In this study the Pro2 residue of EM-2 was modified systematically through substitution by hydroxyproline (Hyp), (S)-?-homoproline (?Pro), 2-aminocyclopentene-1-carboxylic acid (?Acpc) or 2-aminocyclohexene-1-carboxylic acid (?Achc) to obtain stable MOP active compounds. Both Hyp2 and ?Pro2 substitution decreased receptor affinity. Analogues incorporating alicyclic ?-amino acids exhibited diverse receptor binding properties, depending on the configuration of the substituent side-chain. (1S,2R)?Acpc2-EM-2 was shown to have MOP affinity and selectivity comparable to those of EM-2 and proved to act as agonist, while being resistant to proteolysis. NMR and molecular dynamics (MD) studies revealed that bent backbone structures are predominant in the most potent analogues, while their presence is less pronounced in ligands of lower receptor affinity.
Tárgyszavak:	Természettudományok Kémiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban Peptide Endomorphin-2 opioid receptor NMR spectroscopy molecular dynamics (MD) simulations
Megjelenés:	Journal Of Medicinal Chemistry. - 55 : 19 (2012), p. 8418-8428. -
További szerzők:	Mallareddy, Jayapal Reddy Timári István (1989-) (vegyész) Kövér Katalin, E. (1956-2023) (vegyész) Keresztes Attila Tóth Géza
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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001-es BibID:	BIBFORM006201
Első szerző:	Keresztes Attila
Cím:	New endomorphin analogues containing alicyclic beta-amino acids : influence on bioactive conformation and pharmacological profile / Keresztes, A., Szucs, M., Borics, A., Kover, K. E., Forro, E., Fulop, F., Tomboly, C., Peter, A., Pahi, A., Fabian, G., Muranyi, M., Toth, G.
Dátum:	2008
ISSN:	0022-2623
Megjegyzések:	Endomorphins were subjected to a number of structural modifications in a search for their bioactive conformations. The alicyclic beta-amino acids cis-(1S,2R)ACPC/ACHC, cis-(IR,2S)ACPC/ACHC, trans(IS,2S)ACPC/ACHC, and trans-(1R,2R)ACPC/ACHC were introduced into endomorphins to examine the conformational effects on the bioactivity. Use of a combination of receptor binding techniques, H-1 NMR, and molecular modeling allowed the conclusion that Pro(2) substitution by these residues causes changes in structure, proteolytic stability, and pharmacological activity. It seems that the size of the alicyclic beta-amino acids does not have marked influence on the receptor binding affinities and/or selectivities. Among the new analogues, the cis-(1S,2R)ACPC(2) and cis-(1S,2R)ACHC(2)-containing derivatives displayed the highest binding potencies and efficacies in receptor binding and ligand-stimulated [S-35]GTP gamma S functional experiments. Molecular dynamic simulations and H-1 NMR studies of the cis-ACPC/ACHC-containing analogues revealed that many conformations are accessible, though it is most likely that these peptides bind to the mu-opioid receptor in a compact, folded structure rather than extended.
Tárgyszavak:	Természettudományok Kémiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:	Journal Of Medicinal Chemistry. - 51 : 14 (2008), p. 4270-4279. -
További szerzők:	Szűcs Mária Borics Attila Kövér Katalin, E. (1956-2023) (vegyész) Forró Enikő Fülöp Ferenc Tömböly Csaba Péter Antal Páhi Annamária Fábián Gabriella Murányi Mariann Tóth Géza
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001-es BibID:	BIBFORM018784
Első szerző:	Mallareddy, Jayapal Reddy
Cím:	Design, Synthesis, Pharmacological Evaluation, and Structure-Activity Study of Novel Endomorphin Analogues with Multiple Structural Modifications / Jayapal Reddy Mallareddy, Attila Borics, Attila Keresztes, Katalin E. Kövér, Dirk Tourwé, Géza Tóth
Dátum:	2011
ISSN:	0022-2623
Megjegyzések:	ABSTRACT: This study reports on new proteolyticallystable, pharmacologically active endomorphin analogues,incorporating Dmt1, Achc2, pFPhe4, or ?MePhe4 unnaturalamino acids. Consistent with earlier results, it was foundthat the analogues carrying Dmt1 and Achc2 residuesdisplayed the highest ?-opioid receptor affinities, dependingupon the configuration of the incorporated Achc2.Combination of such derivatives with pFPhe4 or ?MePhe4yielded further compounds with variable binding potencies. Combined application of Dmt1, cis-(1S,2R)Achc2, and pFPhe4(compound 16) resulted in the most potent analogue. Ligand stimulated [35S]GTP?S binding assays indicated that the analoguesretained their agonist activities and opioid receptor specificities. NMR and molecular modeling studies of the analogues containing?MePhe4 or pFPhe4 confirmed the predominance of bent structures, however, it is apparent that bent structures are energeticallymore favored than random/extended structures for all studied compounds.
Tárgyszavak:	Természettudományok Kémiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:	Journal Of Medicinal Chemistry. - 54 : 5 (2011), p. 1462-1472. -
További szerzők:	Borics Attila Keresztes Attila Kövér Katalin, E. (1956-2023) (vegyész) Tourwe, Dirk Tóth Géza
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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