Search for new synthetic immunosuppressants II. Tetrazole analogues of hymenistatin I

Linear and cyclic hymenistatin I (HS I) analogues with dipeptide segments Ile2-Pro3, Pro3-Pro4 and Val6-Pro7 replaced by their tetrazole analogues Ile-Ψ[CN4]-Ala3, Pro3-Ψ[CN4]-Ala4 and Val6-Ψ[CN4]-Alawere synthesized by the solid phase peptide synthesis method and cyclized with the TBTU and/or HATU reagent. The peptides were examined for their immunosuppressive activity in the lymphocyte proliferation test (LPT)

Aptamer-based multiplexed proteomic technology for biomarker discovery

Interrogation of the human proteome in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology. We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 [mu]L of serum or plasma). Our current assay allows us to measure ~800 proteins with very low limits of detection (1 pM average), 7 logs of overall dynamic range, and 5% average coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding DNA aptamer concentration signature, which is then quantified with a DNA microarray. In essence, our assay takes advantage of the dual nature of aptamers as both folded binding entities with defined shapes and unique sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD). We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to discover unique protein signatures characteristic of various disease states. More generally, we describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of evidence-based medicine

Plasma Proteomic Profiling in HIV-1 Infected Methamphetamine Abusers

We wanted to determine whether methamphetamine use affects a subset of plasma proteins in HIV-infected persons. Plasma samples from two visits were identified for subjects from four groups: HIV+, ongoing, persistent METH use; HIV+, short-term METH abstinent; HIV+, long term METH abstinence; HIV negative, no history of METH use. Among 390 proteins identified, 28 showed significant changes in expression in the HIV+/persistent METH+ group over the two visits, which were not attributable to HIV itself. These proteins were involved in complement, coagulation pathways and oxidative stress. Continuous METH use is an unstable condition, altering levels of a number of plasma proteins

Fusion of metabolomics and proteomics data for biomarkers discovery: case study on the experimental autoimmune encephalomyelitis

Contains fulltext : 91843.pdf (publisher's version ) (Open Access)12 p

The 42nd Symposium Chromatographic Methods of Investigating Organic Compounds : Book of abstracts

The 42nd Symposium Chromatographic Methods of Investigating Organic Compounds : Book of abstracts. June 4-7, 2019, Szczyrk, Polan

Polimery w macierzach peptydowych/białkowych

Peptide and protein arrays have gained increasing attention due to their potential application in many areas of research, clinical diagnosis, and pharmacy. A typical array consists of asupport containing immobilized peptides or proteins positioned in an addressable format. The greatest advantage of the arrays is the possibility for miniaturization, which relies on dividing the surface into miniature spots, thus allowing for hundreds/thousands of analyses to be simultaneously performed using minimal amounts of aprecious biological material. The quality of assays with the use of peptide and protein arrays depends on the surface properties, e.g., hydrophilicity, homogeneity, density of functional groups, surface morphology, etc. In recent years, it was shown that the quality of the assays might be improved by introducing polymers acting as spacers between the peptide and the solid support. This approach causes changes in the surface properties, e.g., it reduces the undesirable non-specific adsorption of biomolecules, increases the density of functional groups, or can improve the biological activity of biomolecules attached to the surface. In this review, various types of polymers that are used for peptide and protein arrays and their impact on the assay quality are discussed.Peptydy lub białka naniesione w regularnych, uporządkowanych pozycjach na nośnik stały tworzą tzw. macierze. Układy takie wzbudzają coraz większe zainteresowanie, ponieważ można je wykorzystywać do prowadzenia analiz w biochemii, diagnostyce klinicznej czy farmacji. Największą zaletą macierzy jest możliwość miniaturyzacji. Podział powierzchni macierzy na mikroplamki (mikrospoty) pozwala na wykonywanie do kilkuset analiz jednocześnie z wykorzystaniem minimalnej ilości cennego materiału biologicznego. Jakość analiz przeprowadzanych przy użyciu macierzy peptydowych i białkowych zależy od takich właściwości powierzchni, jak: hydrofilowość, jednorodność, gęstość obsadzenia grupami funkcyjnymi, morfologia, itp. W ostatnich latach wykazano, że można poprawić jakość analiz w wyniku wprowadzenia polimerów między peptyd/białko a podłoże. Polimery zmieniają właściwości powierzchni macierzy, np. redukują niepożądaną adsorpcję biocząsteczek, zwiększają gęstość obsadzenia powierzchni grupami funkcyjnymi lub poprawiają dostępność biocząsteczek związanych z powierzchnią. W niniejszej pracy omówiono różne typy polimerów stosowane do otrzymywania macierzy peptydowych i białkowych oraz ich wpływ na jakość przeprowadzanych analiz