1. Synthesis of Met-enkephalin by solution-phase peptide synthesis methodology utilizing para-toluene sulfonic acid as N-terminal masking of l-methionine amino acid
Riaz A Khan Chem Biol Drug Des. 2016 Dec;88(6):884-888. doi: 10.1111/cbdd.12821. Epub 2016 Aug 20.
The Met-enkephalin, Tyr-Gly-Gly-Phe-Met, was synthesized by the solution-phase synthesis (SPS) methodology employing -OBzl group as carboxyls' protection, while the t-Boc groups were employed for the N-terminal α-amines' protection for the majority of the amino acids of the pentapeptide sequence. The l-methionine (l-Met) amino acid was used as PTSA.Met-OBzl obtained from the simultaneous protection of the α-amino, and carboxyl group with para-toluene sulfonic acid (PTSA) and as-OBzl ester, respectively in a C-terminal start of the 2 + 2 + 1 fragments condensation convergent synthetic approach. The protection strategy provided a short, single-step, simultaneous, orthogonal, nearly quantitative, robust, and stable process to carry through the protected l-methionine and l-phenylalanine coupling without any structural deformities during coupling and workups. The structurally confirmed final pentapeptide product was feasibly obtained in good yields through the current approach.
2. A concise and scalable route to L-azidohomoalanine
Stefanie Roth, William C Drewe, Neil R Thomas Nat Protoc. 2010 Dec;5(12):1967-73. doi: 10.1038/nprot.2010.164. Epub 2010 Nov 18.
A concise and highly efficient synthetic route to L-azidohomoalanine (L-Aha) and its homologues is presented here. These chemically modified amino acids are used for the introduction of bioorthogonal handles into proteins. The described route avoids major problems of previously reported methods including expensive starting materials, low efficiency, and lack of scalability. Starting from inexpensive N-Boc-O-Bn-L-aspartic acid, gram quantities of L-Aha hydrochloride can be prepared with high purity. The reactions can be completed within 1 week and the products can be incorporated into proteins using L-methionine auxotrophs.
3. Synthesis, structural characterization, and evaluation of new peptidomimetic Schiff bases as potential antithrombotic agents
Satheesh Chikkanahalli Eranna, Raghavendra Kumar Panchangam, Jayanna Kengaiah, Suchetan Parameshwar Adimule, Sabine Foro, Devaraju Sannagangaiah Monatsh Chem. 2022;153(7-8):635-650. doi: 10.1007/s00706-022-02936-6. Epub 2022 Jul 14.
New Schiff bases functionalized with amide and phenolic groups synthesized by the condensation of 2-hydroxybenzaldehyde and 2-hydroxyacetophenone with amino acid amides which in turn were prepared in two steps from N-Boc-amino acids and homoveraltrylamine through intermediate compounds N-Boc-amino acids amides. The compounds were characterized by elemental analysis, FT-IR, UV-Vis, and NMR spectroscopy. The crystal structures of three Schiff bases were determined by single crystal X-ray diffraction. There exists O-H ⋯ N, N-H ⋯ O, and C-H ⋯ O types of hydrogen bonds and C-H ⋯ π secondary bonding interactions in these crystalline solids. The Schiff bases have been screened for anticoagulant and antiplatelet aggregation activities. All the compounds showed procoagulant activity which shortens the clotting time of citrated human plasma in both platelet-rich plasma and platelet-poor plasma except the derivatives of L-methionine which showed anticoagulant activity by prolonging the clotting time. In addition, the compounds derived from benzyl cysteine and phenylalanine showed adenosine diphosphate induced antiplatelet aggregation activity, whereas others did not show any role. Moreover, all these compounds revealed non-hemolytic activity with red blood cells. Supplementary information: The online version contains supplementary material available at 10.1007/s00706-022-02936-6.
