@article {45708, title = {(R-X-R)(4)-Motif peptides containing conformationally constrained cyclohexane-derived spacers: effect on cellular uptake}, journal = {ChemMedChem}, volume = {12}, year = {2017}, month = {NOV }, pages = {1743-1747}, type = {Article}, abstract = {

Arginine-rich peptides having the (R-X-R) n motif are among the most effective cell-penetrating peptides (CPPs). Herein we report a several-fold increase in the efficacy of such CPPs if the linear flexible spacer (-X-) in the (R-X-R) motif is replaced by constrained cyclic 1,4-substituted-cyclohexane-derived spacers. Internalization of these oligomers in mammalian cell lines was found to be an energy-dependent process. Incorporation of these constrained, non-proteinogenic amino acid spacers in the CPPs is shown to enhance their proteolytic stability.

}, keywords = {(R-X-R)-motif, cell-penetrating peptides, cellular uptake, protease stability}, issn = {1860-7179}, doi = {10.1002/cmdc.201700498}, author = {Bhosle, Govind S. and Fernandes, Moneesha} }