Peripheral reactions dynamics

Although not a taxane, ixabepilone is a novel microtubule inhibitor that was recently approved for metastatic breast cancer in combination with the oral fluoropyrimidine capecitabine or as monotherapy. It is a semisynthetic analog of epothilone B, and is active in the M phase of the cell cycle. This agent binds directly to 6-tubulin subunits on microtubules, leading to inhibition of normal microtubule dynamics. Of note, this agent continues to have activity in drug-resistant tumors that overexpress P-glycoprotein or tubulin mutations. The main adverse effects include myelosuppression, hypersensitivity reactions, and neurotoxicity in the form of peripheral sensory neuropathy. 

Lipoproteins are soluble complexes of proteins (apolipoproteins) and lipids that transport lipids in the circulation of all vertebrates and even insects. Lipoproteins are synthesized in the liver and the intestines, arise from metabolic changes of precursor lipoproteins, or are assembled at the cell membranes from cellular lipids and exogenous lipoproteins or apolipoproteins. In the circulation, lipoproteins are highly dynamic. They undergo enzymatic reactions of their lipid components, facilitated and spontaneous lipid transfers, transfers of soluble apolipoproteins, and conformational changes of the apolipoproteins in response to the compositional changes. Finally, lipoproteins are taken up and catabolized in the liver, kidney, and peripheral tissues via receptor-mediated endocytosis and other mechanisms. This chapter deals with the composition and structure of human lipoproteins. 

Peripheral dynamics is the pictorial term for describing steric hindrance by the central atom (or group). The impact parameter is the miss-distance with respect to the center of mass. Hence, unlike what is often tiie case, here low-impact-parameter collisions are unfavorable because they tend to direct tiie attacking atom toward the wrong target. Reaction is thus preferred for higher impact parameters that sample the periphery of the central atom. Figure 10.14 shows the case of the H + HI H2 + I colhsion as an example. 

---