dc.contributor.author |
Ötvös, László |
|
dc.contributor.author |
Vetter SW |
|
dc.contributor.author |
Koladia M |
|
dc.contributor.author |
Knappe D |
|
dc.contributor.author |
Schmidt R |
|
dc.contributor.author |
Ostorházi, Eszter |
|
dc.contributor.author |
Kovalszky, Ilona |
|
dc.contributor.author |
Bionda N |
|
dc.contributor.author |
Cudic P |
|
dc.contributor.author |
Surmacz E |
|
dc.contributor.author |
Wade JD |
|
dc.contributor.author |
Hoffmann R |
|
dc.date.accessioned |
2016-11-23T13:31:20Z |
|
dc.date.available |
2016-11-23T13:31:20Z |
|
dc.date.issued |
2014 |
|
dc.identifier |
84898927167 |
|
dc.identifier.citation |
pagination=873-882;
journalVolume=46;
journalIssueNumber=4;
journalTitle=AMINO ACIDS; |
|
dc.identifier.uri |
http://repo.lib.semmelweis.hu//handle/123456789/2963 |
|
dc.identifier.uri |
doi:10.1007/s00726-013-1650-6 |
|
dc.description.abstract |
The leptin receptor antagonist peptide Allo-aca exhibits picomolar activities in various cellular systems and sub-mg/kg subcutaneous efficacies in animal models making it a prime drug candidate and target validation tool. Here we identified the biochemical basis for its remarkable in vivo activity. Allo-aca decomposed within 30 min in pooled human serum and was undetectable beyond the same time period from mouse plasma during pharmacokinetic measurements. The C max of 8.9 mug/mL at 5 min corresponds to approximately 22 % injected peptide present in the circulation. The half-life was extended to over 2 h in bovine vitreous fluid and 10 h in human tears suggesting potential efficacy in ophthalmic diseases. The peptide retained picomolar anti-proliferation activity against a chronic myeloid leukemia cell line; addition of a C-terminal biotin label increased the IC50 value by approximately 200-fold. In surface plasmon resonance assays with the biotin-labeled peptide immobilized to a NeutrAvidin-coated chip, Allo-aca exhibited exceptionally tight binding to the binding domain of the human leptin receptor with k a = 5 x 105 M-1 s-1 and k diss = 1.5 x 10-4 s-1 values. Peptides excel in terms of high activity and selectivity to their targets, and may activate or inactivate receptor functions considerably longer than molecular turnovers that take place in experimental animals. |
|
dc.relation.ispartof |
urn:issn:0939-4451 |
|
dc.title |
The designer leptin antagonist peptide Allo-aca compensates for short serum half-life with very tight binding to the receptor |
|
dc.type |
Journal Article |
|
dc.date.updated |
2015-12-07T14:19:17Z |
|
dc.language.rfc3066 |
en |
|
dc.identifier.mtmt |
2502512 |
|
dc.identifier.wos |
000333241800007 |
|
dc.identifier.pubmed |
24366600 |
|
dc.contributor.department |
SE/AOK/I/I. Sz. Patológiai és Kísérleti Rákkutató Intézet |
|
dc.contributor.department |
SE/AOK/K/Bőr-, Nemikórtani és Bőronkológiai Klinika |
|
dc.contributor.institution |
Semmelweis Egyetem |
|