Site-specific incorporation of unnatural amino acids into proteins, both in vivo and in
vitro, is a promising technology with tremendous potential to advance studies in protein
structure and function. The technique allows the incorporation of a vast diversity of
functional groups that extends beyond the conventional mutagenesis of the twenty common
amino acids. The rapid development of orthogonal PylRS/PylT pairs has resulted in an
increasing number of novel unnatural amino acids that can be site-specifically introduced
into proteins. This dissertation presents the syntheses of several unnatural amino acids for use
in protein labeling and activation.
A bipyridine lysine was synthesized for the assembly of metal-binding proteins and
its genetic encoding is shown. In addition, unnatural amino acids bearing reactive
functionalities for bioconjugation reactions for the selective labeling of proteins were
assembled. These include a variety of lysine analogs that can be applied to
carbonyl/aminooxy condensations, thiol-ene reactions, and Diels-Alder cycloadditions.
Moreover, bioorthogonal reaction partners such as aminooxy dyes, thiol, and tetrazine probes
for subsequent protein labeling were prepared.
For the photoregulation of protein activity in live cells, several caged tyrosine analogs
were synthesized. The assembly of caged phosphoryl tyrosines to study tyrosine
د محمد محمود محمد عبد الفتاح | DR MOHAMMAD MAHMOUD MOHAMMAD ADEL FATAH | 9785