1. Synthesis of the novel pi-(benzyloxymethyl)-protected histidine analogue of statine. Inhibition of penicillopepsin by pepstatin-derived peptides containing different statine side-chain derivatives
J Maibaum, D H Rich J Med Chem. 1989 Jul;32(7):1571-6. doi: 10.1021/jm00127a028.
The synthesis of aspartic proteinase inhibitors derived from a new histidine side-chain analogue of statine (Sta), (3S,4S)-4-amino-3-hydroxy-5-(imidazol-4-yl)pentanoic acid (HiSta, 20), is reported. Boc-HiSta(BOM)-OMe (7) was prepared in 16% overall yield from Boc-His(pi-BOM)-OH via formation of the tetramic acid derivative 11 and stereoselective cis reduction with NaBH4 to the 4-hydroxy lactam 12. Removal of the Boc group from ester 7 (enantiomeric purity ee = 88-90%) and coupling to the tripeptide segment Iva-Val-Val-OH (13) by the DCC/HOBt preactivation method followed by hydrogenolytic removal of the pi-BOM group over Pd(OH)2 on carbon gave Iva-Val-Val-HiSta-OMe (16). This new peptide 16 is a very potent inhibitor of the fungal aspartic proteinase penicillopepsin (Ki = 4.5 x 10(-9) M) that is 10 times more active than the comparable Sta-containing inhibitor 3 and 2-3 times more potent than the new (3S,4S)-4-amino-3-hydroxy-5-phenylpentanoic acid (AHPPA) analogue 17 (Ki = 1.5 x 10(-8) M). However, compound 16, which has an imidazole residue at the P1 position, is a significantly weaker inhibitor of the enzyme than the corresponding analogues with the lysine (5) and ornithine (6) side chains at P1. Considerations that led to the synthesis of 16 and the results of the enzyme kinetics are discussed in detail.
2. Comparison of Color Development Kinetics of Tanning Reactions of Dihydroxyacetone with Free and Protected Basic Amino Acids
Yufa Sun, Subin Lee, Long Lin ACS Omega. 2022 Dec 1;7(49):45510-45517. doi: 10.1021/acsomega.2c06124. eCollection 2022 Dec 13.
Sunless tanning has become incredibly prevalent due to the increasing fashionable demand and the awareness of photodamage risks. The brown pigments are induced by dihydroxyacetone (DHA) and amino groups in the stratum corneum (SC) of skin via the Maillard reaction. While most studies concerning sunless tanning reactions have focused on free amino acids (AAs), little information is available on the impact of the side chain of AAs or proteins on this important reaction in cosmetic chemistry. To explore the reactivity and color development kinetics of different types of amino groups, three basic free AAs (Arg, His, and Lys) and three Nα-protected AAs (Boc-Arg-OH, Boc-His-OH, and Boc-Lys-OH) were used to react with DHA using a simplified model system at different reaction times, pH, and temperatures. Full factorial experiments were employed to design and analyze the effects of these three factors. The browning intensity and color characteristics were quantitatively evaluated. The factorial experiments showed that temperature had the most significant influence on the browning intensity and played a dominant role in the interactions with the reaction time and pH. It was found, for the first time, that Arg and His reacted with DHA more rapidly than Boc-Arg-OH and Boc-His-OH, while Boc-Lys-OH developed a stronger color than Lys under the same conditions, suggesting that ε-NH2 of a lysine residue in peptides or proteins of SC may play a crucial role in the color development of DHA tanning. This study not only clearly illustrates the capability of the side chain of AAs to produce colored compounds but also provides a deeper understanding of DHA tanning.
3. Peptide conformational imprints enhanced the catalytic activity of papain for esterification
Kiran Reddy Kanubaddi, Ching-Lun Yang, Pei-Yu Huang, Chung-Yin Lin, Dar-Fu Tai, Chia-Hung Lee Front Bioeng Biotechnol. 2022 Aug 16;10:943751. doi: 10.3389/fbioe.2022.943751. eCollection 2022.
Peptide conformational imprints (PCIs) offer a promising perspective to directly generate binding sites for preserving enzymes with high catalytic activity and stability. In this study, we synthesized a new chiral cross-linker cost-effectively for controlling the matrix morphology of PCIs on magnetic particles (PCIMPs) to stabilize their recognition capability. Meanwhile, based on the flank part of the sequences on papain (PAP), three epitope peptides were selected and synthesized. Molecularly imprinted polymers (MIPs) were then fabricated in the presence of the epitope peptide using our new cross-linker on magnetic particles (MPs) to generate PCIMPs. PCIMPs were formed with helical cavities that complement the PAP structure to adsorb specifically at the targeted position of PAP. PCIMPs65-79 were found to have the best binding parameters to the PAP with K d = 0.087 μM and B max = 4.56 μM. Upon esterification of N-Boc-His-OH, proton nuclear magnetic resonance (1H-NMR) was used to monitor the yield of the reaction and evaluate the activity of PAP/PCIMPs. The kinetic parameters of PAP/PCIMPs65-79 were calculated as V max = 3.0 μM s-1, K m = 5 × 10-2 M, k cat = 1.1 × 10-1 s-1, and k cat/K m = 2.2 M-1 s-1. In addition, PAP is bound tightly to PCIMPs to sustain its activity after four consecutive cycles.
