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Perfluorophenyl Derivatives as Unsymmetrical Linkers for Solid Phase Conjugation.

ABSTRACT: Linkers play major roles in conjugation chemistry toward the advancement of drug discovery. Two different series of fluorinated linkers were introduced to the backbone of a model peptide using solid phase peptide synthesis. These fluorinated linkers have the potential to conjugate two asymmetrical groups. This has not been done using other fluorinated linkers. This study deals with application of linkers with S, N, and O terminals and reports on the investigation of their chemoselectivity and activity for branching peptide backbones using a chosen model peptide. These fluorinated linkers have unique properties that will make it possible for a large diversity of bioconjugated chemicals for different bioapplications to be designed and synthesized.

SUBMITTER: Alapour S

PROVIDER: S-EPMC6279949 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Solid-phase synthesis and kinetic characterization of fluorogenic enzyme-degradable hydrogel cross-linkers.

Project description:Of critical importance in drug delivery and tissue engineering applications is the degradability of implanted polymeric materials. The use of peptide-derived cross-linkers in hydrogel design is a valuable approach by which polymeric carriers can be endowed with enzymatic degradability in a predictable, "programmable" fashion. The solid-phase synthesis strategy described herein allows for an expeditious, flexible synthesis of bis-acrylamide-derivatized peptides with complex modifications, as exemplified by the incorporation of fluorophore and quencher moieties into a matrix metalloprotease (MMP)-degradable cross-linker. The crude synthetic product was obtained in high yield and purity and purified by standard methods; it was then used directly for polymerization without the need for tedious and often nonchemoselective solution-phase modifications. Functional appendages incorporated for detection provided a direct, quantitative link between enzymatic activity and hydrogel degradation using routine methods for identification of optimal enzyme-specific degradability.

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An Alkyne-functionalized Arginine for Solid-Phase Synthesis Enabling "Bioorthogonal" Peptide Conjugation.

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Engineering Enzyme-Cleavable Oligonucleotides by Automated Solid-Phase Incorporation of Cathepsin B Sensitive Dipeptide Linkers.

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Protein-Nucleic Acid Conjugation with Sterol Linkers Using Hedgehog Autoprocessing.

Project description:Hedgehog (Hh) precursor proteins contain an autoprocessing domain called HhC whose native function is protein cleavage and C-terminal glycine sterylation. The transformation catalyzed by HhC occurs in cis from a precursor protein and exhibits wide tolerance toward both sterol and protein substrates. Here, we repurpose HhC as a 1:1 protein-nucleic acid ligase, with the sterol serving as a molecular linker. A procedure is described for preparing HhC-active sterylated DNA, called steramers, using aqueous compatible chemistry and commercial reagents. Steramers have KM values of 7-11 μM and reaction t1/2 values of ∼10 min. Modularity of the HhC/steramer method is demonstrated using four different proteins along with structured and unstructured sterylated nucleic acids. The resulting protein-DNA conjugates retain the native solution properties and biochemical function. Unlike self-tagging domains, HhC does not remain fused to the conjugate; rather, enzymatic activity is mechanistically coupled to conjugate release. That unique feature of HhC, coupled with efficient kinetics and substrate tolerance, may ease access and open new applications for these suprabiological chimeras.

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Conjugation of Doxorubicin to siRNA Through Disulfide-based Self-immolative Linkers.

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New Alkyne and Amine Linkers for Versatile Multiple Conjugation of Oligonucleotides.

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| S-EPMC7807750 | biostudies-literature

Investigation on the compositions of unsymmetrical dimethylhydrazine treatment with different oxidants using solid-phase micro-extraction-gas chromatography-mass spectrometer.

Project description:The majority of unsymmetrical dimethylhydrazine (UDMH) treatments produce lots of toxic by-products, among which N-Nitrosodimethylamine (NDMA) is a strong carcinogen. The compositions of the by-products are important for evaluating the treatment efficiency and understanding the UDMH degradation mechanism to achieve UDMH mineralization. The intermediate and end products of UDMH treatment with different oxidants were investigated by using a simple and fast method, solid-phase micro-extraction (SPME) in combination with gas chromatography-mass spectrometry (GC-MS). The effects of several parameters (coating fibre, salt addition, pH, sampling time and desorption time) were studied to optimize analyte recovery. The best response can be attained by the 65 µm PDMS/DVB fibre at pH 7 during 10 min after desorption of 1 min in the GC inlet. The intermediate and final oxidative products of UDMH wastewater treatment with different oxidants (O3, Mn2+/O3, Fe2+/H2O2) were investigated. The results showed that the UDMH treatment with O3 could lead to high yields of NDMA. Metal catalytic ozonation could largely minimize the formation of NDMA. No NDMA was observed in the final decontaminated samples after treatment with Fe2+/H2O2. The NDMA formation and degradation mechanism were discussed based on the intermediates. This study is expected to provide useful information for controlling NDMA formation during UDMH wastewater treatment.

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