62 research outputs found
Simultaneous cyclization and derivatization of peptides using cyclopentenediones
Unprotected linear peptides containing N-terminal cysteines and another cysteine residue can be simultaneously cyclized and derivatized using 2,2-disubstituted cyclopentenediones. High yields of cyclic peptide conjugates may be obtained in short reaction times using only a slight excess of the cyclopentenedione moiety under TEMPO catalysis and in the presence of LiCl
Stepwise SolidâPhase Synthesis of Nucleopeptides
Phosphodiesterâlinked peptideâoligonucleotide conjugates (nucleopeptides) are obtained by stepwise solidâphase procedures. The peptide is first assembled on a suitably derivatized solid matrix and the oligonucleotide is subsequently elongated at the free hydroxyl group of the linking amino acid. Temporary acidâlabile and permanent baseâlabile protecting groups are combined. Careful choice of the protection scheme is required to prevent and minimize side reactions that may degrade the target molecule.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152587/1/cpnc0422.pd
Straightforward synthesis of cyclic and bicyclic peptides
Cyclic peptide architectures can be easily synthesized from cysteine-containing peptides with appending maleimides, free or protected, through an intramolecular Michael-type reaction. After peptide assembly, the peptide can cyclize either during the trifluoroacetic acid treatment, if the maleimide is not protected, or upon deprotection of the maleimide. The combination of free and protected maleimide moieties and two orthogonally protected cysteines gives access to structurally different bicyclic peptides with isolated or fused cycles
Orthogonal protection of peptides and peptoids for cyclization by the thiol-ene reaction and conjugation
Cyclic peptides and peptoids were prepared using the thiol-ene Michael-type reaction. The linear precursors were provided with additional functional groups allowing for subsequent conjugation: an orthogonally protected thiol, a protected maleimide, or an alkyne. The functional group for conjugation was placed either within the cycle or in an external position. The click reactions employed for conjugation with suitably derivatized nucleoside or oligonucleotides were either cycloadditions (Diels-Alder, Cu(I)-catalyzed azide-alkyne) or the same Michael-type reaction as for cyclization
Diels-Alder cycloadditions in water for the straightforward preparation of peptideâoligonucleotide conjugates
The Diels-Alder reaction between diene-modified oligonucleotides and maleimide-derivatized peptides afforded peptideâoligonucleotide conjugates with high purity and yield. Synthesis of the reagents was easily accomplished by on-column derivatization of the corresponding peptides and oligonucleotides. The cycloaddition reaction was carried out in mild conditions, in aqueous solution at 37°C. The speed of the reaction was found to vary depending on the size of the reagents, but it can be completed in 8â10 h by reacting the diene-oligonucleotide with a small excess of maleimide-peptide
Exploiting protected maleimides to modify oligonucleotides, peptides and peptide nucleic acids
This manuscript reviews the possibilities offered by 2,5-dimethylfuran-protected maleimides. Suitably derivatized building blocks incorporating the exo Diels-Alder cycloadduct can be introduced at any position of oligonucleotides, peptide nucleic acids, peptides and peptoids, making use of standard solid-phase procedures. Maleimide deprotection takes place upon heating, which can be followed by either Michael-type or Diels-Alder click conjugation reactions. However, the one-pot procedure in which maleimide deprotection and conjugation are simultaneously carried out provides the target conjugate more quickly and, more importantly, in better yield. This procedure is compatible with conjugates involving oligonucleotides, peptides and peptide nucleic acids. A variety of cyclic peptides and oligonucleotides can be obtained from peptide and oligonucleotide precursors incorporating protected maleimides and thiols
Solution structure and stability of a disulfide cross-linked nucleopeptide duplex
NMR methods are used to study the structure and stability of the duplex formed by the nucleopeptide [Ac- Cys- Gly- Ala-Hse( p(3')dGCATGC)- Ala-OH](2)[S-S], in which the oligonucleotide is self-complementary and the cysteine residues of the two peptide chains form a disulfide bridge; thermal transitions and NMR-derived structural calculations are consistent with a 3-D structure in which the oligonucleotide forms a standard B-DNA helix without significant distortions; the peptide chains are relatively disordered in solution and lie in the minor groove of the DNA helix; this nucleopeptide duplex exhibits a high melting temperature, indicating that peptide - oligonucleotide conjugates containing cysteines are suitable molecules to establish cross-links between DNA strands and stabilize the duplex
Retro-1-oligonucleotide conjugates. Synthesis and biological evaluation
Addition of small molecule Retro-1 has been described to enhance antisense and splice switching oligonucleotides. With the aim of assessing the effect of covalently linking Retro-1 to the biologically active oligonucleotide, three different derivatives of Retro-1 were prepared that incorporated a phosphoramidite group, a thiol or a 1,3-diene, respectively. Retro-1-oligonucleotide conjugates were assembled both on-resin (coupling of the phosphoramidite) and from reactions in solution (Michael-type thiol-maleimide reaction and Diels-Alder cycloaddition). Splice switching assays with the resulting conjugates showed that they were active but that they provided little advantage over the unconjugated oligonucleotide in the well-known HeLa Luc705 reporter system
Simultaneous cyclization and derivatization of peptides using cyclopentenediones
Unprotected linear peptides containing N-terminal cysteines and another cysteine residue can be simultaneously cyclized and derivatized using 2,2-disubstituted cyclopentenediones. High yields of cyclic peptide conjugates may be obtained in short reaction times using only a slight excess of the cyclopentenedione moiety under TEMPO catalysis and in the presence of LiCl
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