Abstract: The present invention lies in the technical field of enzymatic (poly)peptide ligation and specifically relates to methods that allow the ligation of (poly)peptides and oligonucleotides. The methods comprise providing at least one cargo molecule modified with a peptide tag and at least one poly(peptide) to be ligated to the cargo molecule, wherein the peptide tag and/or the (poly)peptide comprises a ligation motif for a peptide ligase, preferably sortase and peptidyl asparaginyl ligases (PALs), such as butelase-1, VyPAL2 or OaAEPI b. The invention also relates to the resulting conjugates and the corresponding uses.

Abstract: The present invention relates to conjugates comprising (a) an antisense oligonucleotide (ASO) and (b) at least one G-quadruplex structure, wherein the ASO and the at least one G-quadruplex structure are heterologous to each other. The G-quadruplex of the conjugate may be further conjugated with ligands or functional moieties for addressable delivery and enhanced properties including potency and therapeutic index. Further encompassed are such conjugates for use as a medicament, a method of modulating the stability, translation, splicing, cleavage, or activity of a target nucleic acid molecule using such conjugates, and use of G-quadruplex in stabilizing antisense oligonucleotides.

Abstract: The present invention relates to conjugates comprising (a) an antisense oligonucleotide (ASO) and (b) at least one G-quadruplex structure, wherein the ASO and the at least one G-quadruplex structure are heterologous to each other. The G-quadruplex of the conjugate may be further conjugated with ligands or functional moieties for addressable delivery and enhanced properties including potency and therapeutic index. Further encompassed are such conjugates for use as a medicament, a method of modulating the stability, translation, splicing, cleavage, or activity of a target nucleic acid molecule using such conjugates, and use of G-quadruplex in stabilizing antisense oligonucleotides.

Abstract: A method for the generation of a G-quadruplex structure on a target nucleic acid sequence is presented. The approach combines the specificity of Watson-Crick base pair with the stability associated with a robust G-quadruplex scaffold. The induction of such bimolecular quadruplex-duplex hybrids can be applied within the antigene or antisense context for enhanced steric blockage to the transcriptional or translational machinery. In addition, such structures provide unique features for ligand design. This approach also allows the site-specific generation of G-quadruplex structures within nucleic acid nanoarchitectures.

Abstract: A peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1 or a derivative thereof is provided. Also provided are conjugates of such a peptide, the use of the peptide or the conjugates as a medicament, and methods for the detection of parallel-stranded G-quadruplexes.

Abstract: This invention relates to a nucleic acid nanoparticle comprising at least one G-quadruplex structure wherein at least one guanine base comprises a modification in the N2-position and the use of said nucleic acid nanoparticle as a medicament, molecular sensor, or tag. Further this invention relates to methods of stabilizing a nucleic acid nanoparticle comprising at least one G-quadruplex structure.

Abstract: This invention relates to a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1 or a derivative thereof. The present invention also relates to conjugates of said peptide, the use of the peptide or the conjugate as a medicament and to methods for the detection of parallel-stranded G-quadruplexes.

Abstract: A method for the generation of a G-quadruplex structure on a target nucleic acid sequence is presented. The approach combines the specificity of Watson-Crick base pair with the stability associated with a robust G-quadruplex scaffold. The induction of such bimolecular quadruplex-duplex hybrids can be applied within the antigene or antisense context for enhanced steric blockage to the transcriptional or translational machinery. In addition, such structures provide unique features for ligand design. This approach also allows the site-specific generation of G-quadruplex structures within nucleic acid nanoarchitectures.