Linked Life Data

19447619

Source:http://linkedlifedata.com/resource/pubmed/id/19447619

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
2009-7-13
pubmed:abstractText
Aeruginosins are a family of naturally occurring oligopeptides that share a common bicyclic amino acid core structure. Many compounds in the family are inhibitors of serine proteases, such as thrombin and trypsin. Thrombin is an important enzyme in the blood coagulation cascade, and is a promising target for anticoagulant drug development. In order to understand the structure-activity relationship (SAR) and to find selective thrombin inhibitors, we synthesized a series of aeruginosin 298-A analogs, in which the P(2) bicyclic amino acid was replaced by a L-proline residue. The structure optimization was focused on modification of the P(1) position. In choosing the P(1) group, an effort was made to avoid using the highly basic guanidine groups present in nearly all naturally occurring aeruginosins. The synthesis and enzyme assays of these aeruginosin analogs against thrombin and trypsin are reported. We found that several compounds with neutral P(1) groups exhibit excellent selectivity over trypsin and good potency against thrombin. The SAR data of the P(1) groups obtained here can be used in preparing other thrombin inhibitors with better selectivity against trypsin.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1464-3405
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3798-803
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Preparation of L-proline based aeruginosin 298-A analogs: optimization of the P1-moiety.
pubmed:affiliation
Department of Chemistry, University of New Orleans, New Orleans, LA 70148, USA. gwang2@uno.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't