Disease relevance of Hemiasterlin

• The basis of resistance to a synthetic analogue of hemiasterlin, HTI-286 (HTI), was examined in cell populations derived from ovarian carcinoma (A2780/1A9) cells selected in HTI-286 [1].

High impact information on Hemiasterlin

• Hemiasterlin is a potent antimitotic peptide that interferes with microtubule dynamics at picomolar concentrations in cell culture [2].
• HTI-286, a synthetic analogue of the tripeptide hemiasterlin, is a potent antimicrotubule agent that circumvents P-glycoprotein-mediated resistance in vitro and in vivo [3].
• Hemiasterlin is a natural product derived from marine sponges that, like other structurally diverse peptide-like molecules, binds to the Vinca-peptide site in tubulin, disrupts normal microtubule dynamics, and, at stoichiometric amounts, depolymerizes microtubules [3].
• A synthetic analogue of the tripeptide hemiasterlin, designated HTI-286, depolymerizes microtubules, is a poor substrate for P-glycoprotein, and inhibits the growth of paclitaxel-resistant tumors in xenograft models [4].
• Two photoaffinity analogues of the tripeptide, hemiasterlin, exclusively label alpha-tubulin [4].

Biological context of Hemiasterlin

• Structure-based identification of the binding site for the hemiasterlin analogue HTI-286 on tubulin [5].
• Inhibition of hepatic tumor cell proliferation in vitro and tumor growth in vivo by taltobulin, a synthetic analogue of the tripeptide hemiasterlin [6].

Anatomical context of Hemiasterlin

• Modifications of the D-piece carboxylic acid group of the hemiasterlin analog HTI-286 gave tubulin inhibitors which were potent cytotoxic agents in taxol resistant cell lines expressing P-glycoprotein [7].

Associations of Hemiasterlin with other chemical compounds

• Fluorescence correlation spectroscopy (FCS) was applied to investigate the stability of tubulin rings that result from the interaction of alpha beta-tubulin dimers with three vinca domain-binding peptides--cryptophycin 1, hemiasterlin, and dolastatin 10 [8].
• Interactions of the sponge-derived antimitotic tripeptide hemiasterlin with tubulin: comparison with dolastatin 10 and cryptophycin 1 [9].
• The conformation of HTI-286 (I) in complex with the protein was determined from TRNOESY/ROESY experiments and is similar to the X-ray crystal structure conformation observed for hemiasterlin methyl ester in the absence of protein [10].

Analytical, diagnostic and therapeutic context of Hemiasterlin

• An analogue of the naturally occurring tripeptide hemiasterlin, taltobulin (HTI-286, 3), has advanced to clinical trials [11].

References