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Insights on specialty building blocks, conjugation chemistry, process questions, and material selection
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57 articles in total
In Vivo Antibody-ADC Click Reframes Modular Conjugation Design
The reported system uses two bioorthogonal handles. An EGFR-targeting antibody, panitumumab, is modified with trans-cyclooctene (TCO). A HER2-directed ADC, trastuzumab deruxtecan (T-DXd), is modified with tetrazine. The antibody is dosed first, followed 24 hours later by the tetrazine-bearing ADC. The two components are then covalently connected through inverse electron demand Diels-Alder (IEDDA) chemistry.
Reported Pyridine Platform for Sequential Amine–Cysteine Conjugation
The platform uses two differentiated leaving groups on one pyridine ring. In the first operation, a primary amine replaces fluorine through nucleophilic aromatic substitution (SNAr), installing an amine-bearing linker, payload, PEG chain, or other functional unit while the thianthrenium group remains in place. In the second operation, a cysteine thiol displaces thianthrenium to create the aryl-sulfur connection.
Reported Bioisostere Patterns: From Fragment Swaps to Property Goals
Bioisosteric replacement is most useful when a team begins with a defined liability: an oxidative soft spot, an unsuitable polarity range, a hydrolysis-prone group, an interaction that lacks selectivity, or a ring system that limits accessible chemical space. The reported survey organizes possible responses into single-atom edits, functional-group replacements, aromatic-ring changes, and saturated or bicyclic scaffolds.
ADC Downstream Purification: Match TFF and Chromatography to the Impurity
Tangential flow filtration (TFF) can concentrate an ADC, exchange buffer, and remove permeable species such as salts, solvents, quench reagents, and monomeric linker-payload. It cannot provide high-resolution separation among ADC molecules that differ mainly in drug-to-antibody ratio (DAR), surface charge, conformation, or aggregation state. Those species are generally retained together by a membrane selected to retain the antibody.
Oligonucleotide Safety Starts With Chemistry and Conjugate Control
Oligonucleotide therapeutics are not one uniform safety problem. Their behavior depends on backbone chemistry, sugar modifications, sequence, conjugation strategy, delivery route, and tissue distribution. That is why FDA clinical pharmacology guidance for oligonucleotide therapeutics calls out immunogenicity risk, hepatic and renal impairment, QTc assessment, and drug-drug interaction considerations as development topics.
Multi-Target GLP-1 Peptides Raise Peptide Process Chemistry Questions
Single-molecule incretin programs have moved from GLP-1-only designs toward dual and triple receptor concepts. For a chemistry team, the useful question is not whether one clinical program will outperform another; it is how added receptor biology changes the molecule that must be assembled, modified, purified, and characterized.