The aim of this review is to make researchers aware of the benefits of an efficient quality control system for prediction of a developed vaccine's efficacy. Two major goals should be addressed when inactivating a virus for vaccine purposes: first, the infectious virus should be inactivated completely in order to be safe, and second, the viral epitopes important for the induction of protective immunity should be conserved after inactivation in order to have an antigen of high quality. Therefore, some problems associated with the virus inactivation process, such as virus aggregate formation, protein crosslinking, protein denaturation and degradation should be addressed before testing an inactivated vaccine in vivo
A prototype sphingomyelin stationary phase for Immobilized Artificial Membrane (IAM) chromatography was synthesized by an ultra-short, solid-phase inspired methodology, in which an oxidative release monitoring strategy played a vital role. Evaluated in a proof-of-concept model for blood-brain barrier passage, partial least squares regression demonstrated its potential as an in vitro prediction tool.
Over the past decades, several in vitro methods have been tested for their ability to predict drug penetration across the blood-brain barrier. So far, in high-performance liquid chromatography, most attention has been paid to micellar liquid chromatography and immobilized artificial membrane (IAM) LC. IAMLC has been described as a viable approach, since the stationary phase emulates the lipid environment of a cell membrane. However, research in IAMLC has almost exclusively been limited to phosphatidylcholine (PC)-based stationary phases, even though PC is only one of the lipids present in cell membranes. In this article, sphingomyelin and cholester stationary phases have been tested for the first time towards their ability to predict drug penetration across the blood-brain barrier. Upon comparison with the PC stationary phase, the sphingomyelin- and cholester-based columns depict similar predictive performance. Combining data from the different stationary phases did not lead to improvements of the models.
Miniature versions of basic leucine zipper (bZIP) and basic helix–loop–helix zipper (b‐HLH‐ZIP) transcription factors are promising tools for molecular dissection of the genetic information in a post‐genomic context. Despite the opportunities of genome interfering agents based on certain oncogenic zipper proteins, structural mimicry of transcription factors is a delicate undertaking, and experimental fine‐tuning through bottom‐up organic chemistry could benefit from solid‐phase/library approaches. Involved in a variety of human pathologies, we became interested in the miniaturization of the cMyc‐Max b‐HLH‐ZIP oncoprotein, and herein elaborate on our synthetic progress in that direction. A bile acid scaffold was successfully employed as artificial dimerization interface in this new type of transcription factor model. Orthogonality of the applied Alloc/Boc/Fmoc chemistries allowed the synthesis of both homo‐ and heterodimeric peptidosteroid conjugates, covalently restricted with defined geometrical properties. Recognition peptides were assembled through standard Fmoc/tBu solid‐phase peptide synthesis (SPPS) chemistry, assisted by automated procedures for consecutive chain elongation on solid support. Invaluable to monitor present strategy, a photocleavable linker allowed rapid, yet detailed analysis of side chain protected peptide intermediates, liberated from the sampled resin, by reverse‐phase HPLC and MALDI‐TOF‐MS. By decorating each scaffold position with two basic region peptides in a 2 × 2 design, a first generation of unprecedented b(‐HLH‐)ZIP peptidosteroids was efficiently obtained. As such, a versatile methodology amenable to library generation is presented.
With the study of peptides and proteins at the heart of many scientific endeavors, the omics era heralded a multitude of opportunities for chemists and biologists alike. Across the interface with life sciences, peptide chemistry plays an indispensable role, and progress made over the past decades now allows proteins to be treated as molecular patchworks stitched together through synthetic tailoring. The continuous elaboration of sophisticated strategies notwithstanding, Merrifield's solid-phase methodology remains a cornerstone of chemical protein design. Although the non-practitioner might misjudge peptide synthesis as trivial, routine, or dull given its long history, we comment here on its many advances, obstacles, and prospects from a practitioner's point of view. While sharing our perspectives through thematic highlights across the literature, this treatise provides an interpretive overview as a guide to novices, and a recap for specialists.
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