1. Facile solid-phase synthesis of sulfated tyrosine-containing peptides: total synthesis of human big gastrin-II and cholecystokinin (CCK)-39
K Kitagawa, C Aida, H Fujiwara, T Yagami, S Futaki, M Kogire, J Ida, K Inoue J Org Chem. 2001 Jan 12;66(1):1-10. doi: 10.1021/jo000895y.
Chemical synthesis of tyrosine O-sulfated peptides is still a laborious task for peptide chemists because of the intrinsic acid-lability of the sulfate moiety. An efficient cleavage/deprotection procedure without loss of the sulfate is the critical difficulty remaining to be solved for fluoren-9-ylmethoxycarbonyl (Fmoc)-based solid-phase synthesis of sulfated peptides. To overcome the difficulty, TFA-mediated solvolysis rates of a tyrosine O-sulfate [Tyr(SO3H)] residue and two protecting groups, tBu for the hydroxyl group of Ser and 2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl (Pbf) for the guanidino group of Arg, were examined in detail. The desulfation obeyed first-order kinetics with a large entropy (59.6 J.K-1.mol-1) and enthalpy (110.5 kJ.mol-1) of activation. These values substantiated that the desulfation rate of the rigidly solvated Tyr(SO3H) residue was strongly temperature-dependent. By contrast, the SN1-type deprotections were less temperature-dependent and proceeded smoothly in TFA of a high ionizing power. Based on the large rate difference between the desulfation and the SN1-type deprotections in cold TFA, an efficient deprotection protocol for the sulfated peptides was developed. Our synthetic strategy for Tyr(SO3H)-containing peptides with this effective deprotection protocol is as follows: (i) a sulfated peptide chain is directly constructed on 2-chlorotrityl resin with Fmoc-based solid-phase chemistry using Fmoc-Tyr(SO3Na)-OH as a building block; (ii) the protected peptide-resin is treated with 90% aqueous TFA at 0 degree C for an appropriate period of time for the cleavage and deprotection. Human cholecystokinin (CCK)-12, mini gastrin-II (14 residues), and little gastrin-II (17 residues) were synthesized with this method in 26-38% yields without any difficulties. This method was further applied to the stepwise synthesis of human big gastrin-II (34 residues), CCK-33 and -39. Despite the prolonged acid treatment (15-18 h at 0 degree C), the ratios of the desulfated peptides were less than 15%, and the pure sulfated peptides were obtained in around 10% yields.
2. Photo-Curable Lacquer Sap Resin Based on Urushiol-Mimicking, Tyrosine-Containing Additive
Jiwon Park, Seon-Mi Jin, Avnish Kumar Mishra, Jung Ah Lim, Eunji Lee Langmuir. 2022 Aug 16;38(32):10010-10021. doi: 10.1021/acs.langmuir.2c01422. Epub 2022 Aug 7.
Oriental lacquer sap is attracting considerable attention as a renewable and eco-friendly natural resin with high durability, heat resistance, insulation, insect repellency, and antiseptic and antibacterial properties. However, to ensure excellent coating performance, it is necessary to improve the drying/curing process of lacquer sap with a time-consuming drying time at high humidity [relative humidity (RH), 70-90%] and ambient temperature (20-30 °C). Drawing on an understanding of the polymerization mechanism of urushiol, the main component of the lacquer sap consisted of a water-in-oil (W/O) emulsion, and this study presents an eco-friendly additive that mimics the structure-function of urushiol composed of a polar catechol head group and a nonpolar hydrocarbon tail. A photo-curable lacquer sap was thus developed by adding a tyrosine amino acid-based lipid agent (denoted as Y-ADDA), which allows faster and more effective drying/curing at lower humidity while maintaining the nature-derived properties of lacquer sap. Y-ADDA easily coassembles with urushiol in the W/O emulsion droplets, thereby significantly accelerating the formation of a polymer network along with urushiol during water evaporation leading to fast drying/curing under ultraviolet (UV) light irradiation at low humidity (~50% RH). The UV-cured lacquer sap resins showed higher performance in terms of film processing and physicochemical properties compared with that of the lacquer containing only tyrosine amino acids without aliphatic tail conjugation, N-(9-fluorenylmethoxycarbonyl)-O-tert-butyl-l-tyrosine Fmoc-Tyr(tBu)-OH. Furthermore, the drying and curing times, film morphology, transmittance, hardness, and adhesion strength of the UV-cured lacquer were markedly superior compared to those of shellac, a general eco-friendly fast-drying primer. The study provides useful strategies and insights to promote the industrial application of lacquer sap resins by employing biocompatible nanoagents developed with an understanding of the curing mechanism of natural resins and from the viewpoint of green and sustainable chemistry perspective.
