170080-13-4Relevant articles and documents
Constraining the Side Chain of C-Terminal Amino Acids in Apelin-13 Greatly Increases Affinity, Modulates Signaling, and Improves the Pharmacokinetic Profile
Tran, Kien,Van Den Hauwe, Robin,Sainsily, Xavier,Couvineau, Pierre,C?té, Jér?me,Simard, Louise,Echevarria, Marco,Murza, Alexandre,Serre, Alexandra,Théroux, Léa,Saibi, Sabrina,Haroune, Lounès,Longpré, Jean-Michel,Lesur, Olivier,Auger-Messier, Mannix,Spino, Claude,Bouvier, Michel,Sarret, Philippe,Ballet, Steven,Marsault, éric
supporting information, p. 5345 - 5364 (2021/02/16)
Side-chain-constrained amino acids are useful tools to modulate the biological properties of peptides. In this study, we applied side-chain constraints to apelin-13 (Ape13) by substituting the Pro12 and Phe13 positions, affecting the binding affinity and signaling profile on the apelin receptor (APJ). The residues 1Nal, Trp, and Aia were found to be beneficial substitutions for Pro12, and the resulting analogues displayed high affinity for APJ (Ki 0.08-0.18 nM vs Ape13 Ki 0.7 nM). Besides, constrained (d-Tic) or α,α-disubstituted residues (Dbzg; d-α-Me-Tyr(OBn)) were favorable for the Phe13 position. Compounds 47 (Pro12-Phe13 replaced by Aia-Phe, Ki 0.08 nM) and 53 (Pro12-Phe13 replaced by 1Nal-Dbzg, Ki 0.08 nM) are the most potent Ape13 analogues activating the Gα12 pathways (53, EC50 Gα12 2.8 nM vs Ape13, EC50 43 nM) known to date, displaying high affinity, resistance to ACE2 cleavage as well as improved pharmacokinetics in vitro (t1/2 5.8-7.3 h in rat plasma) and in vivo.
Preparation method for 2-amino-3-biphenylpropionic acid
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Paragraph 0026; 0032; 0033; 0039; 0040; 0046, (2019/10/01)
The invention discloses a preparation method for 2-amino-3-biphenylpropionic acid. The preparation method comprises the following steps: step 1, with p-bromobenzaldehyde and phenylboronic acid as rawmaterials and an organic solvent as a reaction solvent, subjecting the p-bromobenzaldehyde and the phenylboronic acid to a reaction under the actions of alkali and a catalyst so as to obtain biphenylcarbaldehyde (II); step 2, allowing the biphenylcarbaldehyde (II) to react with ethyl cyanoacetate under the action of the alkali so as to obtain an intermediate (III); step 3, allowing the intermediate (III) to generate a reduction reaction with hydrogen under the catalytic action of Pd/C in a hydrogen atmosphere so as to obtain an intermediate (IV); step 4, allowing the intermediate (IV) to be hydrolyzed into an amide compound (V) in absolute ethyl alcohol under the action of the alkali; and step 5, subjecting the amide compound (V) to a reaction under the actions of bromine and sodium hydroxide so as to obtain the 2-amino-3-biphenylpropionic acid. The preparation method provided by the invention has the advantages of cheap and easily-available raw materials, low production cost, short reaction steps, mild reaction conditions, convenient post-treatment, high yield and applicability to industrial production.
Single-Biocatalyst Synthesis of Enantiopure d-Arylalanines Exploiting an Engineered d-Amino Acid Dehydrogenase
Parmeggiani, Fabio,Ahmed, Syed T.,Thompson, Matthew P.,Weise, Nicholas J.,Galman, James L.,Gahloth, Deepankar,Dunstan, Mark S.,Leys, David,Turner, Nicholas J.
, p. 3298 - 3306 (2016/10/20)
A practical and efficient biocatalytic synthesis of aromatic d-amino acids has been developed, based on the reductive amination of the corresponding α-keto acids via a recombinant whole cell system composed of an engineered dehydrogenase and cofactor recycling apparatus. The reaction was shown to give excellent enantioselectivity (≥98%) and good yields at the preparative scale across a broad range of substrates. Additionally, the structure of the variant enzyme was solved to allow rationalisation of the observed reaction rates. The engineered whole cell catalyst was also used to mediate the production of d-phenylalanine derivatives from racemic mixtures and cheaper l-amino acids by combining it with an enantiocomplementary deaminase. (Figure presented.).
