#
# arev:/usr/local/unicat/unireq/beamreq/req00156.txt
# UNICAT Member Beam Time Request  #156

# created Mon Dec 18 16:02:14 CST 2000
#

collaboration:
	No

collaborator+Pete:
	on

contact:
	boukarih@mail.nih.gov

days:
	3

description:
	Tubulin protein polymers (microtubules) are central to cell division and consequently are the target of many anti-cancer drugs.  Recently, a new class of VINCA domain natural-product drugs have been found, and are being tested in preclinical and early clinical trials.  These compounds are novel in that they destabilize microtubules, and induce tubulin ring polymers.  Electron micrographs and SANS data both 
	reveal single-walled rings with diameters ranging from 27 to 47 nm depending on the drug. Last year, we performed complementary USAXS experiments at the UNICAT USAXS instrument to characterize further the structure of these polymers.  Surprisingly, we observed the formation of sizable monodisperse aggregates (~7 microns) presumably from these rings.  Only one set of solution
	conditons (pH=7.0 and ionic strength 0.1) was examined, and under these conditions the aggregates were observed with one drug(Dolastatin) only. Subsequent light scattering experiments show that the other drugs can also induce such aggregation in solution conditions of lower pH.  In the present proposed experiments we plan to perform additional USAXS experiments with Dolastatin as well as the other drugs (Cryptophysin and Hemiasterlin)with solutions prepared with different parameters (pH and ionic strength) to charaterize the structuture of these aggregates.  Because of the size ranges of these aggregates USAXS is the appropriate technique to probe the aggregation process induced by these important new tubulin-binding drugs.

equipment+required:
	USAXS instrument only.

experiment:
	 USAXS studies of drug-induced tubulin ring polymers

foreign+nationals:
	

hazards:
	No Hazards

name:
	Hacene Boukari

new+request:
	on

nonmembers:
	D. L. Sackett  (NICHD, NIH, Bethesda, Maryland).
	H. Boukari (NICHD, NIH, Bethesda, Maryland).
	R. J. Nossal (NICHD, NIH, Bethesda, Maryland).
	

station:
	33ID-D

unacceptable+dates:
	02/16-02/22/01



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