169396-88-7Relevant articles and documents
Synthesis and characterization of cationic PNA bearing 5-ω-aminopropyl-uracil
Kim, Paul H.,Switzer, Christopher
, p. 5580 - 5582 (2014)
5-ω-Aminopropyl-uracil bearing PNA monomers are synthesized for solid phase oligomer synthesis using FMOC protection. Several PNA oligomers with differing amounts of aminopropyluracil modification were prepared. These oligomers were found to associate with complementary DNA oligonucleotides.
Bioactivity improvement via display of the hydrophobic core of HYD1 in a cyclic β-hairpin-like scaffold, MTI-101
Jain, Priyesh,Badger, David B.,Liang, Yi,Gebhard, Anthony W.,Santiago, Daniel,Murray, Philip,Kaulagari, Sridhar R.,Gauthier, Ted J.,Nair, Rajesh,Kumar, MohanRaja,Guida, Wayne C.,Hazlehurst, Lori A.,McLaughlin, Mark L.
, (2020/10/12)
HYD1 is an all D-amino acid linear 10-mer peptide that was discovered by one-bead-one-compound screening. HYD1 has five hydrophobic amino acids flanked by polar amino acids. Alanine scanning studies showed that alternating hydrophobic amino acid residues and N- and C-terminal lysine side chains were contributors to the biological activity of the linear 10-mer analogs. This observation led us to hypothesize that display of the hydrophobic pentapeptide sequence of HYD1 in a cyclic beta-hairpin-like scaffold could lead to better bioavailability and biological activity. An amphipathic pentapeptide sequence was used to form an antiparallel strand and those strands were linked via dipeptide-like sequences selected to promote β-turns. Early cyclic analogs were more active but otherwise mimicked the biological activity of the linear HYD1 peptide. The cyclic peptidomimetics were synthesized using standard Fmoc solid phase synthesis to form linear peptides, followed by solution phase or on-resin cyclization. SAR studies were carried out with an aim to increase the potency of these drug candidates for the killing of multiple myeloma cells in vitro. The solution structures of 1, 5, and 10 were elucidated using NMR spectroscopy. 1H NMR and 2D TOCSY studies of these peptides revealed a downfield Hα proton chemical shift and 2D NOE spectral analysis consistent with a β-hairpin-like structure.
In search of visible-light photoresponsive peptide nucleic acids (PNAs) for reversible control of DNA hybridization
Zhang, Lei,Linden, Greta,Vázquez, Olalla
, p. 2500 - 2508 (2019/12/11)
Photoswitchable oligonucleotides can determine specific biological outcomes by light-induced conformational changes. In particular, artificial probes activated by visible-light irradiation are highly desired in biological applications. Here, we report two novel types of visible-light photoswitchable peptide nucleic acids (PNAs) based on the molecular transducers: hemithioindigo and tetra-ortho-fluoroazobenzene. Our study reveals that the tetra-ortho-fluoroazobenzene–PNA conjugates have promising properties (fast reversible isomerization, exceptional thermal stability, high isomer conversions and sensitivity to visible-light irradiation) as reversible modulators to control oligonucleotide hybridization in biological contexts. Furthermore, we verified that this switchable modification delivers a slightly different hybridization behavior in the PNA. Thus, both melting experiments and strand-displacement assays showed that in all the cases the trans-isomer is the one with superior binding affinities. Alternative versions, inspired by our first compounds here reported, may find applications in different fields such as chemical biology, nanotechnology and materials science.
