The development of solid phase peptide synthesis has released tremendous opportunities for using synthetic peptides in medicinal applications. In the last decades, peptide therapeutics became an emerging market in pharmaceutical industry. The need for synthetic strategies in order to improve peptidic properties, such as longer half-life, higher bioavailability, increased potency and efficiency is accordingly rising. In this mini-review, we present a toolbox of modifications in peptide chemistry for overcoming the main drawbacks during the transition from natural peptides to peptide therapeutics. Modifications at the level of the peptide backbone, amino acid side chains and higher orders of structures are described. Furthermore, we are discussing the future of peptide therapeutics development and their impact on the pharmaceutical market. 相似文献
Introduction: Mass spectrometry (MS) is widely used in the characterization of biomolecules including peptide and protein therapeutics. These biotechnology products have seen rapid growth over the past few decades and continue to dominate the global pharmaceutical market. Advances in MS instrumentation and techniques have enhanced protein characterization capabilities and supported an increased development of biopharmaceutical products.
Areas covered: This review describes recent developments in MS-based biotherapeutic analysis including sequence determination, post-translational modifications (PTMs) and higher order structure (HOS) analysis along with improvements in ionization and dissociation methods. An outlook of emerging applications of MS in the lifecycle of product development such as comparability, biosimilarity and quality control practices is also presented.
Expert commentary: MS-based methods have established their utility in the analysis of new biotechnology products and their lifecycle appropriate implementation. In the future, MS will likely continue to grow as one of the leading protein identification and characterization techniques in the biopharmaceutical industry landscape. 相似文献
PurposeA new polymer gel dosimeter recipe was investigated that may be more suitable for widespread applications than polyacrylamide gel dosimeters, since the extremely toxic acrylamide has been replaced with the less harmful monomer 2-Acrylamido 2-Methyl Propane Sulfonic acid (AMPS).MethodsThe new formulation was named PAMPSGAT. The MRI response (R2) of the dosimeters was analyzed for conditions of varying dose, dose rate, and temperature during scanning. Radiological properties of the PAMPSGAT polymer gel dosimeter were investigated.ResultsThe dose-response (R2) of AMPS/Bis appears to be linear over a dose range 10–40 Gy. The percentage of difference between the R2 values for imaging at 15 °C and MRI room temperature is about 4.6% for vial with 40 Gy absorbed dose which decreased to less than 1% for imaging at 20 °C. The percentage difference of Zeff of PAMPSGAT gel and soft tissue was less than 1% in the practical energy range (100 KeV–100 MeV). The electron density of the PAMPSGAT polymer gel was 2.9% higher than that of muscle. Results showed that the sensitivity of PAMPSGAT polymer gel dosimeter irradiated by 60Co (energy = 1.25 MeV) is about 27.7% higher than that of irradiated using a 6 MeV Linac system.ConclusionsTemperature during MRI scanning has a small effect on the R2 response of the PAMPSGAT polymer gel dosimeter. Results confirmed tissue equivalency of the PAMPSGAT polymer gel dosimeter in most practical energy range. The PAMPSGAT polymer gel dosimeter response depends on energy and dose rate. 相似文献
The present work deals with the assembly of multilayers or rod-like polymers with hydrophobic side chains (called hairy rods)
and their potential application as ultrathin polymer cushions for the build-up of self healing supported membranes on various
solids (Si/SiO2-wafer, gold covered substrates). Three types of hairy rods were studied: Isopentyl cellulose (IPC), phtalocyaniatopolysiloxane
with mixed alkane side chains (PCPS) and trimethylsilane cellulose (TMCS). Detailed analysis of the thickness of supported
multilayers as a function of the number of deposited monolayers with ellipsometry, near infrared surface plasmon resonance
(NIR-SPR), a quartz crystal microbalance (QCM) and reflection interference contrast microscopy (RICM), show that the basic
building blocks of hairy rod multilayers are bilayers with the hydrophobic surfaces of the monolayers facing each other. Continuous
and stable firms of hairy rods can be deposited if the hydrophobicities of the solid surface and the monolayer are matched.
It is demonstrated by lateral diffusion measurements (using photobleaching techniques) that continuous phospholipid bilayers
can be deposited onto multilayers of rigid rods of TMCS after hydrophilization by cleavage of trimethylsilane side chains
in HCl-vapour, while stable lipid monolayers can be deposited onto hydrophobic surfaces of rigid rod layers. NIR-SPR allows
the observation of double band reflectivity curves at interfaces separating different surface layers and thus offers the possibility
of differential detection of ligand binding at the interface of differently functionalized domains.
Received: 2 February 1996 / Accepted: 28 October 1996 相似文献
We have recently demonstrated that a treatment combining the cell differentiating agent sodium butyrate (NaBut) and interleukin-2 (IL2) resulted in a remission of established peritoneal colorectal carcinomatosis in rats. NaBut or IL2 treatment alone, never cured these tumour-bearing rats. In the present investigation, we report that NaBut-treatments induce apoptosis in the colonic cancer cells both in vitro and in vivo. We postulated that the significant therapeutic effect of NaBut/IL2 treatment can be mainly attributed to a NaBut-induced apoptosis of the tumoural cells increasing their immunogenicity. Indeed, treatment which combined apoptotic bodies (apobodies) as cell vaccine, plus IL2 immunotherapy significantly increased tumour remission and survival rate of the vaccinated rats, whereas IL2 treatment alone did not. We observed that the cured rats presented long-term protection against subsequent challenge with the parental tumour cells. This latter result suggests that these treatments generate an immune protection. This was confirmed by the presence, in the sera of the cured rats, of anti-tumoural antibodies directed against both the apobodies and the tumour cells, but not against normal colonocytes. In addition, we show that injections of apobodies before administration of the parental tumour cells results in a partial protection. We provide the first evidence that apobodies, derived from cancer cells after NaBut-treatment, induce a specific immune response against parental tumours cells. These data suggest that the distinctive immunologic properties of apobodies could provide a valuable tool in colorectal cancer immunotherapy. 相似文献
The antitumor effect of ribonucleases was studied with animal ribonucleolytic enzymes, bovine pancreatic RNase A, bovine seminal RNase (BS-RNase), onconase and angiogenin. While bovine pancreatic RNase A exerts a minor antitumor effect, BS-RNase and onconase exert significant effects. Angiogenin, as RNase, works in an opposite way, it initiates vascularization of tumors and subsequent tumor growth. Ribonunclease inhibitors are not able to inhibit the antitumor effectiveness of BS-RNase or onconase. However, they do so in the case of pancreatic RNases. Conjugation of BS-RNase with antibodies against tumor antigens (preparation of immunotoxins) like the conjugation of the enzyme with polymers enhances the antitumor activity of the ribonuclease. After conjugation with polymers, the half-life of BS-RNase in blood is extended and its immunogenicity reduced. Recombinant RNases have the same functional activity as the native enzymes. The synthetic genes have also been modified, some of them with gene sequences typical for the BS-RNase parts. Recent experimental efforts are directed to the preparation of ‘humanized antitumor ribonuclease’ that would be structurally similar to human enzyme with minimal immunogenicity and side effects. The angiogenesis of tumors is attempted to be minimized by specific antibodies or anti-angiogenic substances. 相似文献