FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2093677355> ?p ?o ?g. }

• W2093677355 endingPage "3182" @default.
• W2093677355 startingPage "3175" @default.
• W2093677355 abstract "In an earlier report we identified specific modifications and substitutions of corticotropin releasing factor (CRF) that led to the discovery of antagonists with extended duration of action as compared to that of astressin {cyclo(30-33)[DPhe(12),Nle(21),Glu(30), Lys(33),Nle(38)]hCRF((12)(-)(41))}. These additional modifications included elongation of the peptide chain by three residues at the N-terminus, its acetylation, and the [CalphaMeLeu(27)] substitution to yield cyclo(30-33)[DPhe(12), Nle(21),CalphaMeLeu(27),Glu(30), Lys(33),Nle(38)]Ac-hCRF((9)(-)(41)), which was found to be longer acting than astressin (Rivier, J.; et al. J. Med. Chem. 1998, 41, 5012-5019). To further increase the efficiency (potency, duration of action, and bioavailability) of this family of antagonists, we introduced two or more CalphaMe-leucine residues at positions shown in earlier studies to be favorable (Hernandez, J.-F.; et al. J. Med. Chem. 1993, 36, 2860-2867). Whereas the introduction of CalphaMe-leucine residues at positions 27 and either 18 (11), 37 (17), or 40 (19) resulted in dramatic increases in duration of inhibitory action in the adrenalectomized (adx) rat after intravenous injection, the same substitution at positions 27 and either 15 (7, 8), 17 (9), 19 (12, 13), or 41 (20) led to short acting analogues. Other substitutions by CalphaMeLeu at positions 27 and either 10 (4), 13 (5), 14 (6), 21 (14), 24 (15), 36 (16), or 38 (18) yielded analogues with duration of action intermediate between those mentioned above. Cyclo(30-33)[DPhe(12), Nle(21), CalphaMeLeu(27),Glu(30),Lys(33),Nle(38), CalphaMeLeu(40)]Ac-hCRF((9)(-)(41)) (astressin B, 19) was one of the most efficacious analogues of this series (>4 h inhibition of ACTH secretion at 25 microgram/adx rat). It was found to be even longer acting via subcutaneous administration in either an aqueous (>24 h inhibition of ACTH secretion at 100 microgram/adx rat) or lipid milieu (DMSO/peanut oil, >24 h inhibition of ACTH secretion at 30 microgram/adx rat) than after intravenous administration (<12 h inhibition of ACTH secretion at 100 microgram/adx rat). We concluded that Calpha-methylation at some positions may favor a bioactive conformation while also preventing degradation and/or elimination, resulting in significant extension of duration of action." @default.
• W2093677355 created "2016-06-24" @default.
• W2093677355 creator A5003830977 @default.
• W2093677355 creator A5033348306 @default.
• W2093677355 creator A5041127606 @default.
• W2093677355 creator A5068536947 @default.
• W2093677355 creator A5069663022 @default.
• W2093677355 creator A5082047884 @default.
• W2093677355 date "1999-07-24" @default.
• W2093677355 modified "2023-09-26" @default.
• W2093677355 title "Constrained Corticotropin Releasing Factor Antagonists (Astressin Analogues) with Long Duration of Action in the Rat" @default.
• W2093677355 cites W1493629431 @default.
• W2093677355 cites W1948313709 @default.
• W2093677355 cites W1971210116 @default.
• W2093677355 cites W1971922927 @default.
• W2093677355 cites W1988066423 @default.
• W2093677355 cites W1988069204 @default.
• W2093677355 cites W1990149819 @default.
• W2093677355 cites W1990332976 @default.
• W2093677355 cites W1991192480 @default.
• W2093677355 cites W1993407840 @default.
• W2093677355 cites W2005731408 @default.
• W2093677355 cites W2008690448 @default.
• W2093677355 cites W2010827811 @default.
• W2093677355 cites W2013188356 @default.
• W2093677355 cites W2017168736 @default.
• W2093677355 cites W2019595831 @default.
• W2093677355 cites W2020056822 @default.
• W2093677355 cites W2032725109 @default.
• W2093677355 cites W2033932995 @default.
• W2093677355 cites W2037687950 @default.
• W2093677355 cites W2040989387 @default.
• W2093677355 cites W2044331640 @default.
• W2093677355 cites W2051119043 @default.
• W2093677355 cites W2056231731 @default.
• W2093677355 cites W2077308889 @default.
• W2093677355 cites W2077657226 @default.
• W2093677355 cites W2079377730 @default.
• W2093677355 cites W2087389654 @default.
• W2093677355 cites W2095036452 @default.
• W2093677355 cites W2095317731 @default.
• W2093677355 cites W2142155713 @default.
• W2093677355 cites W2166293213 @default.
• W2093677355 cites W2171846995 @default.
• W2093677355 cites W2466726936 @default.
• W2093677355 cites W4250414022 @default.
• W2093677355 cites W4376848280 @default.
• W2093677355 doi "https://doi.org/10.1021/jm9902133" @default.
• W2093677355 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/10447963" @default.
• W2093677355 hasPublicationYear "1999" @default.
• W2093677355 type Work @default.
• W2093677355 sameAs 2093677355 @default.
• W2093677355 citedByCount "64" @default.
• W2093677355 countsByYear W20936773552012 @default.
• W2093677355 countsByYear W20936773552014 @default.
• W2093677355 countsByYear W20936773552015 @default.
• W2093677355 countsByYear W20936773552016 @default.
• W2093677355 countsByYear W20936773552017 @default.
• W2093677355 countsByYear W20936773552018 @default.
• W2093677355 countsByYear W20936773552022 @default.
• W2093677355 crossrefType "journal-article" @default.
• W2093677355 hasAuthorship W2093677355A5003830977 @default.
• W2093677355 hasAuthorship W2093677355A5033348306 @default.
• W2093677355 hasAuthorship W2093677355A5041127606 @default.
• W2093677355 hasAuthorship W2093677355A5068536947 @default.
• W2093677355 hasAuthorship W2093677355A5069663022 @default.
• W2093677355 hasAuthorship W2093677355A5082047884 @default.
• W2093677355 hasBestOaLocation W20936773552 @default.
• W2093677355 hasConcept C126322002 @default.
• W2093677355 hasConcept C134018914 @default.
• W2093677355 hasConcept C150903083 @default.
• W2093677355 hasConcept C181389837 @default.
• W2093677355 hasConcept C185592680 @default.
• W2093677355 hasConcept C202751555 @default.
• W2093677355 hasConcept C207001950 @default.
• W2093677355 hasConcept C2776120743 @default.
• W2093677355 hasConcept C2779138802 @default.
• W2093677355 hasConcept C2779281246 @default.
• W2093677355 hasConcept C55493867 @default.
• W2093677355 hasConcept C57992300 @default.
• W2093677355 hasConcept C71240020 @default.
• W2093677355 hasConcept C71924100 @default.
• W2093677355 hasConcept C86803240 @default.
• W2093677355 hasConcept C98274493 @default.
• W2093677355 hasConceptScore W2093677355C126322002 @default.
• W2093677355 hasConceptScore W2093677355C134018914 @default.
• W2093677355 hasConceptScore W2093677355C150903083 @default.
• W2093677355 hasConceptScore W2093677355C181389837 @default.
• W2093677355 hasConceptScore W2093677355C185592680 @default.
• W2093677355 hasConceptScore W2093677355C202751555 @default.
• W2093677355 hasConceptScore W2093677355C207001950 @default.
• W2093677355 hasConceptScore W2093677355C2776120743 @default.
• W2093677355 hasConceptScore W2093677355C2779138802 @default.
• W2093677355 hasConceptScore W2093677355C2779281246 @default.
• W2093677355 hasConceptScore W2093677355C55493867 @default.
• W2093677355 hasConceptScore W2093677355C57992300 @default.
• W2093677355 hasConceptScore W2093677355C71240020 @default.
• W2093677355 hasConceptScore W2093677355C71924100 @default.

• next