Linked Life Data

10585209

Source:http://linkedlifedata.com/resource/pubmed/id/10585209

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
2000-1-4
pubmed:abstractText
Parallel and antiparallel heterodimers have been synthesized that combine into a single molecule the neurohypophyseal hormone oxytocin and the potent vasopressin V(2)-antagonist d(CH(2))(5)[D-Ile(2), Ile(4)]arginine vasopressin. Solid-phase synthesis with N(alpha)-9-fluorenylmethyloxycarbonyl (Fmoc) chemistry, featuring appropriate combinations of orthogonal protecting groups for the thiols [S-(N-methyl-N-phenylcarbamoyl)sulfenyl (Snm); S-acetamidomethyl (Acm); S-triphenylmethyl (Trt)], was used to assemble the required linear nonapeptide amide monomer intermediates, which were then brought together in defined ways by solution reactions to provide the two heterodimers. The first disulfide bridge was formed by a directed approach involving attack by the free thiol of the 1-beta-mercapto-beta, beta-cyclopentamethylenepropionic acid (Pmp) residue of one monomer onto the Snm group of a cysteine residue on the other monomer; the inverse directed strategy failed due to steric hindrance. The second disulfide bridge was formed by iodine co-oxidation of Cys(Acm) residues on adjacent chains. Biological studies revealed that both the parallel and antiparallel chimeras lack pressor activity, have low uterotonic activity, and have diuretic activities comparable to that of the monomeric V(2)-antagonist. Sodium excretion depends on experimental conditions. Thus, with a 4% water load, both chimeras display effects similar to that of an equimolar mixture of oxytocin and V(2)-antagonist, i.e., lower sodium excretion than that resulting from administration of oxytocin alone but higher than that when V(2)-antagonist was administered alone. However, when no water load was used, the parallel chimera proved to be more effective in promoting sodium excretion than either oxytocin alone or an equimolar mixture of oxytocin and V(2)-antagonist.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
2
pubmed:volume
42
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5002-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10585209-Amino Acid Sequence, pubmed-meshheading:10585209-Animals, pubmed-meshheading:10585209-Arginine Vasopressin, pubmed-meshheading:10585209-Blood Pressure, pubmed-meshheading:10585209-Cysteine, pubmed-meshheading:10585209-Dimerization, pubmed-meshheading:10585209-Disulfides, pubmed-meshheading:10585209-Diuretics, pubmed-meshheading:10585209-Female, pubmed-meshheading:10585209-Molecular Sequence Data, pubmed-meshheading:10585209-Natriuresis, pubmed-meshheading:10585209-Oxytocin, pubmed-meshheading:10585209-Rats, pubmed-meshheading:10585209-Rats, Wistar, pubmed-meshheading:10585209-Recombinant Fusion Proteins, pubmed-meshheading:10585209-Solutions, pubmed-meshheading:10585209-Structure-Activity Relationship, pubmed-meshheading:10585209-Sulfhydryl Compounds, pubmed-meshheading:10585209-Uterus, pubmed-meshheading:10585209-Vasopressins
pubmed:year
1999
pubmed:articleTitle
Chemical syntheses and biological studies on dimeric chimeras of oxytocin and the V(2)-antagonist, d(CH(2))(5)[D-Ile(2), Ile(4)]arginine vasopressin.
pubmed:affiliation
Departments of Chemistry and Laboratory Medicine & Pathology, University of Minnesota, Minneapolis, Minnesota 55455, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.