@article { ISI:000308042000010,
	title = {Efficient synthesis of a hydroxyethylamine (HEA) isostere and its alpha-aminophosphonate and phosphoramidate derivatives as potential anti-HIV agents},
	journal = {Chemmedchem},
	volume = {7},
	number = {9},
	year = {2012},
	month = {SEP},
	pages = {1601-1611},
	publisher = {WILEY-V C H VERLAG GMBH},
	address = {BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY},
	abstract = {<p>HIV protease is a promising drug target for AIDS therapy, and several potent HIV-1 protease inhibitors have been reported to date. Although existing inhibitors exhibit high selectivity, they have also been associated with severe side effects and the possible emergence of therapeutic resistance. As HIV protease cleaves the peptide bond via a tetrahedral intermediate, various transition-state models such as hydroxyethylamine (HEA) have been designed. We therefore pursued an efficient synthesis of an HEA isostere; this was performed with a novel one-pot reductiontransiminationreduction reaction sequence as a key step. a-Aminophosphonate and phosphoramidate derivatives of the HEA isostere were designed and synthesized, and all of the synthesized derivatives were assayed for their anti-HIV activities against wild-type and mutant HIV strains. Phosphoramidate derivative 15?a was found to be the most active of all synthesized compounds against the IIIB and RES056 strains. As phosphonates are known to exhibit physiological stability, good cell permeability, and other promising pharmacokinetic characteristics, our newly synthesized compounds have the potential as alternatives to existing therapeutics and diagnostics.</p>},
	keywords = {a-aminophosphonates, antiviral agents, hydroxyethylamine isosteres, phosphoramidates, synthesis},
	issn = {1860-7179},
	doi = {10.1002/cmdc.201200271},
	author = {Bhattacharya, Asish K. and Rana, Kalpeshkumar C. and Pannecouque, Christophe and De Clercq, Eric}
}
@article {44188,
	title = {Superior HIV-1 TAR binders with conformationally constrained R52 arginine mimics in the Tat(48-57) peptide},
	journal = {Chemmedchem},
	volume = {13},
	year = {2018},
	month = {FEB },
	pages = {220-226},
	type = {Article},
	abstract = {<p>We report a 100-fold increase in binding affinity of the Tat(48-57) peptide to HIV-1 transcriptional activator-responsive element (TAR) RNA by replacing Arg52, an essential and critical residue for Tat{\textquoteright}s specific binding, with (2S,4S)-4-guanidinoproline. The resulting Tat1M peptide is a far superior binder than Tat1M, a peptide containing another conformationally constrained arginine mimic, (2S,4S)-4-amino-N-(3-guanidinopropyl)proline, or even the control Tat peptide (CtrlTat) itself. Our observations are supported by circular dichroism (CD), isothermal titration calorimetry (ITC), gel electrophoresis and UV spectroscopy studies. Molecular dynamics simulations suggest increased interactions between the more compact Tat1M and TAR RNA, relative to CtrlTat. The CD signature of the RNA itself remains largely unchanged upon binding of the peptides. The Tat mimetics further have better cell uptake properties than the control Tat peptide, thus increasing their potential application as specific TAR-binding molecules.</p>},
	keywords = {antiviral agents, arginine mimics, RNA, Tat peptide analogues, Tat-TAR binding},
	issn = {1860-7179},
	doi = {10.1002/cmdc.201700653},
	author = {Bhosle, Govind S. and Kharche, Shalmali and Kumar, Santosh and Sengupta, Durba and Maiti, Souvik and Fernandes, Moneesha}
}
