Eth Zurich

Philochem Ag

Eidgenossische Technische Hochschule Zurich

Eidgenoessische Technische Hochschule Zurich

Moreno Wichert

Jorg Scheuermann

Dario Neri

Willy Decurtins

Jörg Scheuermann

Nikolaus Krall

Raphael Franzini

This invention relates to the synthesis of nucleic acid-encoded chemical libraries using common adaptor sequences. Nucleic acid strands coupled to chemical moieties may be contacted with identifier oligonucleotides comprising coding sequences encoding the chemical moieties and an adaptor oligonucleotides, such that the adaptor oligonucleotide hybridizes to both the nucleic acid strands and the identifier oligonucleotides to allow ligation of the identifier oligonucleotides to the nucleic acid strands. The adaptor oligonucleotide is then removed. Nucleic acid-encoded chemical libraries, and methods of producing or screening such libraries are provided.

Production of encoded chemical libraries

A binding moiety (B) for Carbonic Anhydrase IX (CAIX), the binding moiety comprising: The binding moiety is univalent, bivalent, or multivalent. A targeted therapeutic agent may comprise the binding moiety. The invention also includes a method for treating a disease expressing elevated levels of CAIX by administering the targeted therapeutic agent.

Small molecule drug conjugates

A targeted therapeutic agent comprising a compound of formula I:B-L-D&#x2003;&#x2003;(I),wherein: B is a low molecular weight binding moiety for Carbonic Anhydrase IX (CAIX); D is a drug moiety; and L is a linker group that undergoes cleavage in vivo for releasing said drug moiety in an active form. The drug moiety is suitably a cytotoxic agent for targeted delivery to cancer cells expressing CAIX. The binding moiety B suitably comprises a sulfonamidothiadiazole moiety. The binding moiety B may comprise one, two or more groups capable of binding to CAIX. The linker group suitably comprises a disulfide bond and/or a triazole group and/or a cleavable peptide group.

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Wangen-Nuolen, Switzerland

Moreno Wichert