Organisation och personal

Rasel Al-Amin

doktorand vid Institutionen för immunologi, genetik och patologi, Molekylära verktyg; Forskargrupp Ulf Landegren

E-post:
rasel.al-amin[AT-tecken]igp.uu.se
Telefon:
018-471 4959
Besöksadress:
BMC, Husargatan 3
751 22 Uppsala
Postadress:
Box 815
751 08 Uppsala

Mina kurser

Forskning

Molecular tools for analysis of drug binding characteristics

Structural similarities in active sites of drug targets lead to risks of poor selectivity and unwanted side effects in rational drug design. There is a great need for more accurate techniques to monitor selective binding and correct localization of a candidate drug and its target interaction in healthy or pathological clinical specimen in the process of drug discovery in preclinical studies. In a first phase, we have developed very sensitive and specific in situ drug-target interaction detection methods TEMA (Target Engagement–Mediated Amplification), where target binding by DNA-linked kinase inhibitors were visualized and quantified in cells and tissues by rolling-circle amplification (RCA) and Pharma-PLA, using the proximity ligation assays mechanism. The methods serve to investigate selective target binding and correct localization of candidate drug in relevant clinical specimen during lead optimization in preclinical drug discovery. Another on going effort is aimed to combine the cellular thermal shift assay (CETSA) with multiplex proximity extension assays (PEA) for quantitative drug proteins interaction analysis. Preliminarily we have developed a CETSA-PEA assay in cell extracts and a next aim is to apply this novel approach in consecutive fresh frozen samples of nucleated blood cells from leukemia patients before and after initiation of targeted therapy.

Publikationer

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