The extracellular matrix plays an important role in many physiological processes. We have identified >20 angiogenic sites in the extracellular matrix protein laminin-1. The most potent sites are A13 (RQVFQVAYIIIKA) and @entity70412 (KAFDITYVRLKF), which are present in homologous @entity2733 -terminal domains of the alpha 1 and gamma 1 chains, respectively. We reported recently that a scrambled @entity70412 sequence, @entity70413 (DFKLFAVTIKYR), acts as an antagonist to both peptides. Here, we have identified a stronger antiangiogenic peptide, @entity70414 ( @entity70413 with a T to Y substitution), with potent activity in several biological assays including @entity5 growth. @entity70414 is more potent in promoting endothelial cell attachment and inhibiting attachment to laminin-1 than either @entity70412 or @entity70414 . Disruption of tube formation by @entity70414 is also observed at concentrations at least five times lower than @entity70413 . The minimal active sequence was found to be DFKLFAVY. @entity70414 is more potent in blocking @entity70412 -induced @entity1573 chorioallantoic membrane angiogenesis than @entity70413 . Tumor growth studies on the @entity1573 chorioallantoic membrane showed that @entity70414 reduces @entity0 without affecting cell proliferation. This result suggests that angiogenesis is being inhibited by the peptide. In vivo animal studies demonstrated that @entity70414 treatment significantly reduced @entity5 growth and @entity5 , as compared with controls, additionally suggesting that angiogenesis was affected. These results indicate that we have identified a more potent antiangiogenesis inhibitor peptide that may be used as a therapeutic to treat @entity5 .

Identification of a potent peptide antagonist to an active laminin-1 sequence that blocks angiogenesis and XXXX growth.

@entity0 :: ('MESH:D001943', 'Disease') :: ['breast cancer cell growth'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'cancer', 'decreased tumor vessel number'] @entity2733 :: ('CHEBI:29345', 'Chemical') :: ['NH(2)'] @entity70412 :: ('404269(Tax:9031)', 'Gene') :: ['C16'] @entity1573 :: ('9031', 'Species') :: ['chick'] @entity70413 :: ('p|SUB|C|16|S', 'ProteinMutation') :: ['C16S'] @entity70414 :: ('p|SUB|C|16|Y', 'ProteinMutation') :: ['C16Y']
@entity5 :: (MESH:D009369,Disease) :: ['tumor']
