A historical overview of peptide chemistry from T. Curtius to E. Fischer to M. Bergmann and L. Zervas is first presented. Next, the fundamentals of peptide synthesis with a focus on solid phase peptide synthesis by R. B. Merrifield are described. Immobilization strategies to attach the first amino acid to the resin, coupling strategies in stepwise peptide chain elongation, and approaches to synthesize difficult peptide sequences are also shown. A brief comparison between tert-butyloxycarbonyl (Boc)/benzyl (Bzl) strategy and 9-fluorenylmethoxycarbonyl (Fmoc)/tert-butyl (t -Bu) strategy utilized in solid phase peptide synthesis is given with an emphasis on the latter. Finally, the review focuses on the discovery and development of peptide ligation and the latest advances in this field including native amide bond formation strategies, these include the native chemical ligation, α-ketoacid-hydroxylamine ligation, and serine/threonine ligation which are the most commonly used chemoselective ligation methods that provide amide bond at the ligation site. This review provides an overview of the literature concerning the most important advances in the chemical synthesis of proteins and peptides covering the period from 1882 to 2017.

With the current outbreak caused by SARS-CoV-2, vaccination is acclaimed as a public health care priority. Rapid genetic sequencing of SARS-CoV-2 has triggered the scientific community to search for effective vaccines. Collaborative approaches from research institutes and biotech companies have acknowledged the use of viral proteins as potential vaccine candidates against COVID-19. Nucleic acid (DNA or RNA) vaccines are considered the next generation vaccines as they can be rapidly designed to encode any desirable viral sequence including the highly conserved antigen sequences. RNA vaccines being less prone to host genome integration (cons of DNA vaccines) and anti-vector immunity (a compromising factor of viral vectors) offer great potential as front-runners for universal COVID-19 vaccine. The proof of concept for RNA-based vaccines has already been proven in humans, and the prospects for commercialization are very encouraging as well. With the emergence of COVID-19, mRNA-1273, an mRNA vaccine developed by Moderna, Inc. was the first to enter human trials, with the first volunteer receiving the dose within 10 weeks after SARS-CoV-2 genetic sequencing. The recent interest in mRNA vaccines has been fueled by the state of the art technologies that enhance mRNA stability and improve vaccine delivery. Interestingly, as per the “Draft landscape of COVID-19 candidate vaccines” published by the World Health Organization (WHO) on December 29, 2020, seven potential RNA based COVID-19 vaccines are in different stages of clinical trials; of them, two candidates already received emergency use authorization, and another 22 potential candidates are undergoing pre-clinical investigations. This review will shed light on the rationality of RNA as a platform for vaccine development against COVID-19, highlighting the possible pros and cons, lessons learned from the past, and the future prospects.

Severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, arose at the end of 2019 as a zoonotic virus, which is the causative agent of the novel coronavirus outbreak COVID-19. Without any clear indications of abatement, the disease has become a major healthcare threat across the globe, owing to prolonged incubation period, high prevalence, and absence of existing drugs or vaccines. Development of COVID-19 vaccine is being considered as the most efficient strategy to curtail the ongoing pandemic. Following publication of genetic sequence of SARS-CoV-2, globally extensive research and development work has been in progress to develop a vaccine against the disease. The use of genetic engineering, recombinant technologies, and other computational tools has led to the expansion of several promising vaccine candidates. The range of technology platforms being evaluated, including virus-like particles, peptides, nucleic acid (DNA and RNA), recombinant proteins, inactivated virus, live attenuated viruses, and viral vectors (replicating and non-replicating) approaches, are striking features of the vaccine development strategies. Viral vectors, the next-generation vaccine platforms, provide a convenient method for delivering vaccine antigens into the host cell to induce antigenic proteins which can be tailored to arouse an assortment of immune responses, as evident from the success of smallpox vaccine and Ervebo vaccine against Ebola virus. As per the World Health Organization, till January 22, 2021, 14 viral vector vaccine candidates are under clinical development including 10 nonreplicating and four replicating types. Moreover, another 39 candidates based on viral vector platform are under preclinical evaluation. This review will outline the current developmental landscape and discuss issues that remain critical to the success or failure of viral vector vaccine candidates against COVID-19.

No abstract

The synthesis of stable glycopeptide mimetics is of particular interest in bioorganic chemistry to allow access of glycoconjugates for biological investigations. In this paper, a straightforward solid‐phase synthesis of a novel glycopeptide mimetic by a Staudinger phosphite reaction is presented. Thereby, a dimethyl phosphite containing peptide, which is obtained by standard phosphitylation of a Ser residue, is treated on the solid support with glycosyl azides, delivering phosphoramidate‐linked glycoconjugates. These artificial glycopeptides show excellent stability under acidic and physiological conditions.