- Synthesis and Characterization of Optically Pure Gamma-PNA Backbones by SIBX-Mediated Reductive Amination
-
Chiral peptide nucleic acid (PNA) is a derivative of regular PNA by introducing a chiral center to its backbone, and is known to bind more strongly to DNA or RNA than regular PNA. In particular, in the case of a γ-backbone, the L isomer stabilizes the PNA/DNA duplex, and the D-isomer has the opposite effect. Therefore, the synthesis of an optically pure γ-backbone is very important. Here, we report a novel synthetic strategy for the suppression of epimerization during the synthesis of the γ-PNA backbone. A stabilized form of 2-iodoxybenzoic acid (SIBX) was used as an oxidative reagent in the key intermediate of the N-Boc-amino acetaldehyde synthesis. This paper reports (1) the synthesis and comparison of three different γ-PNA backbones (lysine, alanine, and glutamate) by three different synthetic routes (SIBX, lithium aluminum hydride, and Red-Al) and (2) the determination of chiral purity from their derivative compounds. The enantiomeric excess purity of SIBX-mediated γ-PNA backbones was determined to be more than 99.4%, as ascertained by the high-performance liquid chromatography (HPLC) chromatogram on a standard RP-C18 column. It is comparatively higher than that of the other methods examined in this work.
- Periyalagan, Alagarsamy,Kim, Yong-Tae,Hong, In Seok
-
p. 1304 - 1309
(2021/08/09)
-
- Multipurpose isothiocyanyl alanine/lysine: Use as solvatochromic IR probes and in site specific labeling/ligation of short peptides
-
The solvatochromic IR responsivity of small side chain –NCS in two unexplored unnatural amino acids, isothiocyanyl alanine (NCSAla = Ita) and lysine (NCSLys = Itl), without perturbing the conformation is demonstrated in two designed
- Bag, Subhendu Sekhar,De, Suranjan
-
supporting information
p. 1404 - 1409
(2018/03/23)
-
- Backbone-Fluorinated 1,2,3-Triazole-Containing Dipeptide Surrogates
-
The 1,2,3-triazole moiety can be incorporated as a peptide bond bioisostere to provide protease resistance in peptidomimetics. Herein, we report the synthesis of peptidomimetic building blocks containing backbone-fluorinated 1,4-disubstituted 1,2,3-triazole moieties. Synthetic protocols for the preparation of various Xaa-Gly dipeptide surrogates in the form of Xaa-ψ[triazole]-F2Gly building blocks were established, and selected examples were introduced into the endogenous peptide opioid receptor ligand Leu-enkephalin as a model compound.
- Engel-Andreasen, Jens,Wellh?fer, Isabelle,Wich, Kathrine,Olsen, Christian A.
-
p. 11613 - 11619
(2017/11/10)
-
- ALIPHATIC PROLINAMIDE DERIVATIVES
-
This invention is directed to novel aliphatic prolinamide derivatives of Formula I, and pharmaceutically acceptable salts, solvates, solvates of the salt and prodrugs thereof, useful in the prevention (e.g., delaying the onset of or reducing the risk of developing) and treatment (e.g., controlling, alleviating, or slowing the progression of) of age-related macular degeneration (AMD) and related diseases of the eye. These diseases include dry-AMD, wet-AMD, geographic atrophy, diabetic retinopathy, retinopathy of prematurity, polypoidal choroidal vasculopathy, and degeneration of retinal or photoreceptor cells. The invention disclosed herein is further directed to methods of prevention, slowing the progress of, and treatment of dry-AMD, wet-AMD, and geographic atrophy, diabetic retinopathy, retinopathy of prematurity, polypoidal choroidal vasculopathy, and degeneration of retinal or photoreceptor cells, comprising: administration of a therapeutically effective amount of compound of the invention. The compounds of the invention are inhibitors of HTRAl. Thus, the compounds of the invention are useful in the prevention and treatment of a wide range of diseases mediated (in whole or in part) by HTRAl. The compounds of the invention are also useful for inhibiting HTRAl protease activity in an eye or locus of an arthritis or related condition.
- -
-
Paragraph 0169; 0170
(2018/04/11)
-
- INHIBITORS OF LYSINE GINGIPAIN
-
The present invention relates generally to therapeutics targeting the bacterium Porphyromonas gingivalis, including its protease Lysine gingipain (Kgp), and their use for the treatment of disorders associated with P. gingivalis infection, including brain disorders such as Alzheimer's disease. In certain embodiments, the invention provides compounds according to Formula I, as described herein, and pharmaceutically acceptable salts thereof.
- -
-
Paragraph 0368; 0370
(2016/05/02)
-
- γ-substituted peptide nucleic acids constructed from L-lysine are a versatile scaffold for multifunctional display
-
(Figure Presented) On display: This model shows DNA (pink) annealed to a peptide nucleic acid (PNA; orange) containing several L-lysine γ side chains (LKγ-PNA) in the middle of the PNA oligomer. The LKγ-PNA side chains project away f
- Englund, Ethan A.,Appella, Daniel H.
-
p. 1414 - 1418
(2008/03/15)
-
- NAcSDKP analogues resistant to angiotensin-converting enzyme
-
Two series of analogues of the tetrapeptide NAcSDKP, an inhibitor of hematopoietic stem cell proliferation, were prepared, and their enzymatic stability toward rabbit lung angiotensin-converting enzyme (ACE) was evaluated as well as their capacity to inhibit NAcSDKP hydrolysis by this enzyme. In the first series, each of the peptide bonds has been successively replaced by an aminomethylene bond. In the second one, the C-terminus of the peptide has been modified by decarboxylation or amidation. The results reported here indicate that all of these molecules but one have good stability toward the enzyme but none of the compounds is able to inhibit NAcSDKP hydrolysis by ACE.
- Gaudron,Adeline,Potier,Thierry
-
p. 3963 - 3968
(2007/10/03)
-