FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2003444313> ?p ?o ?g. }

• W2003444313 endingPage "3427" @default.
• W2003444313 startingPage "3420" @default.
• W2003444313 abstract "Peptide YY (PYY) is a gut hormone that inhibits secretion and promotes absorption and growth in the intestinal epithelium. We have performed structure−activity studies with the active site, N-α-Ac-PYY(22−36)-NH2, for interaction with intestinal PYY receptors. Investigation of aromatic substitutions at position 27 resulted in analogues that exhibited potent in vitro antisecretory potencies with N-α-Ac-[Trp27]PYY(22−36)-NH2 exhibiting even greater potency than intact PYY. In vivo studies in dogs revealed that this analogue also promoted intestinal absorption of water and electrolytes during continuous intravenous and intraluminal infusion. Investigations carried out to identify features that would enhance stability revealed that incorporation of Trp30 increased affinity for PYY receptors. A “CH2-NH” scan revealed that incorporation of reduced bonds at position 28−29 or 35−36 imparted greater receptor affinity. In general, disubstituted analogues designed based on the results of single substitutions exhibited good receptor affinity with N-α-Ac-[Trp27,CH2-NH35-36]PYY(22−36)-NH2 having the greatest affinity (IC50 = 0.28 nM). Conservative multiple substitutions with Nle→Leu and Nva→Val also imparted good affinity. An analogue designed to encompass most of the favored substitutions, N-α-Ac-[Nle24,28,Trp30,Nva31,CH2-NH35-36]PYY(22−36)-NH2, exhibited a proabsorptive effect in dogs comparable to, but longer lasting than, that of intact hormone. Selected analogues also exhibited good antisecretory potencies in rats with N-α-Ac-[Trp30]PYY(22−36)-NH2 being even more potent than PYY. However, the potencies did not correlate well with the PYY receptor affinity or the proabsorptive potencies in dogs. These differences could be due to species effects and/or the involvement of multiple receptors and neuronal elements in controlling the in vivo activity of PYY compounds. PYY(22−36) analogues exhibited good affinity for neuronal Y2 receptors but poor affinity for Y1 receptors. Also, crucial analogues in this series hardly bound to Y4 and Y5 receptors. In summary, we have developed PYY(22−36) analogues which, via interacting with intestinal PYY receptors, promoted potent and long-lasting proabsorptive and antisecretory effects in in vivo models. These compounds or analogues based on them may have useful clinical application in treating malabsorptive disorders observed under a variety of conditions." @default.
• W2003444313 created "2016-06-24" @default.
• W2003444313 creator A5017559214 @default.
• W2003444313 creator A5021809095 @default.
• W2003444313 creator A5024854321 @default.
• W2003444313 creator A5030902481 @default.
• W2003444313 creator A5034324217 @default.
• W2003444313 creator A5037937701 @default.
• W2003444313 creator A5039818487 @default.
• W2003444313 creator A5047821016 @default.
• W2003444313 creator A5059198766 @default.
• W2003444313 creator A5073095140 @default.
• W2003444313 creator A5076634867 @default.
• W2003444313 creator A5082411155 @default.
• W2003444313 creator A5008570413 @default.
• W2003444313 creator A5083160928 @default.
• W2003444313 date "2000-08-04" @default.
• W2003444313 modified "2023-10-17" @default.
• W2003444313 title "Structure−Activity Studies Including a Ψ(CH₂-NH) Scan of Peptide YY (PYY) Active Site, PYY(22−36), for Interaction with Rat Intestinal PYY Receptors: Development of Analogues with Potent in Vivo Activity in the Intestine" @default.
• W2003444313 cites W1518395053 @default.
• W2003444313 cites W177724895 @default.
• W2003444313 cites W1970814454 @default.
• W2003444313 cites W1978331534 @default.
• W2003444313 cites W1995757244 @default.
• W2003444313 cites W1999227915 @default.
• W2003444313 cites W2014653319 @default.
• W2003444313 cites W2017042230 @default.
• W2003444313 cites W2026591624 @default.
• W2003444313 cites W2034178105 @default.
• W2003444313 cites W2034995830 @default.
• W2003444313 cites W2036569119 @default.
• W2003444313 cites W2053573835 @default.
• W2003444313 cites W2056843426 @default.
• W2003444313 cites W2063105437 @default.
• W2003444313 cites W2080115401 @default.
• W2003444313 cites W2091290004 @default.
• W2003444313 cites W2093711076 @default.
• W2003444313 cites W2118132295 @default.
• W2003444313 doi "https://doi.org/10.1021/jm000052z" @default.
• W2003444313 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/10978189" @default.
• W2003444313 hasPublicationYear "2000" @default.
• W2003444313 type Work @default.
• W2003444313 sameAs 2003444313 @default.
• W2003444313 citedByCount "29" @default.
• W2003444313 countsByYear W20034443132013 @default.
• W2003444313 countsByYear W20034443132015 @default.
• W2003444313 countsByYear W20034443132018 @default.
• W2003444313 countsByYear W20034443132020 @default.
• W2003444313 countsByYear W20034443132021 @default.
• W2003444313 countsByYear W20034443132023 @default.
• W2003444313 crossrefType "journal-article" @default.
• W2003444313 hasAuthorship W2003444313A5008570413 @default.
• W2003444313 hasAuthorship W2003444313A5017559214 @default.
• W2003444313 hasAuthorship W2003444313A5021809095 @default.
• W2003444313 hasAuthorship W2003444313A5024854321 @default.
• W2003444313 hasAuthorship W2003444313A5030902481 @default.
• W2003444313 hasAuthorship W2003444313A5034324217 @default.
• W2003444313 hasAuthorship W2003444313A5037937701 @default.
• W2003444313 hasAuthorship W2003444313A5039818487 @default.
• W2003444313 hasAuthorship W2003444313A5047821016 @default.
• W2003444313 hasAuthorship W2003444313A5059198766 @default.
• W2003444313 hasAuthorship W2003444313A5073095140 @default.
• W2003444313 hasAuthorship W2003444313A5076634867 @default.
• W2003444313 hasAuthorship W2003444313A5082411155 @default.
• W2003444313 hasAuthorship W2003444313A5083160928 @default.
• W2003444313 hasConcept C118303440 @default.
• W2003444313 hasConcept C126322002 @default.
• W2003444313 hasConcept C134018914 @default.
• W2003444313 hasConcept C150903083 @default.
• W2003444313 hasConcept C170493617 @default.
• W2003444313 hasConcept C185592680 @default.
• W2003444313 hasConcept C202751555 @default.
• W2003444313 hasConcept C207001950 @default.
• W2003444313 hasConcept C2779281246 @default.
• W2003444313 hasConcept C2780796126 @default.
• W2003444313 hasConcept C55493867 @default.
• W2003444313 hasConcept C56191518 @default.
• W2003444313 hasConcept C57992300 @default.
• W2003444313 hasConcept C71240020 @default.
• W2003444313 hasConcept C71924100 @default.
• W2003444313 hasConcept C86803240 @default.
• W2003444313 hasConcept C93984277 @default.
• W2003444313 hasConceptScore W2003444313C118303440 @default.
• W2003444313 hasConceptScore W2003444313C126322002 @default.
• W2003444313 hasConceptScore W2003444313C134018914 @default.
• W2003444313 hasConceptScore W2003444313C150903083 @default.
• W2003444313 hasConceptScore W2003444313C170493617 @default.
• W2003444313 hasConceptScore W2003444313C185592680 @default.
• W2003444313 hasConceptScore W2003444313C202751555 @default.
• W2003444313 hasConceptScore W2003444313C207001950 @default.
• W2003444313 hasConceptScore W2003444313C2779281246 @default.
• W2003444313 hasConceptScore W2003444313C2780796126 @default.
• W2003444313 hasConceptScore W2003444313C55493867 @default.
• W2003444313 hasConceptScore W2003444313C56191518 @default.
• W2003444313 hasConceptScore W2003444313C57992300 @default.
• W2003444313 hasConceptScore W2003444313C71240020 @default.
• W2003444313 hasConceptScore W2003444313C71924100 @default.
• W2003444313 hasConceptScore W2003444313C86803240 @default.

• next