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The peptide discovery team at IRBM has extensive expertise in chemo-selective conjugation approaches of peptides for a range of different entities (proteins, mAbs, lipids, small molecules, fluorescent labels, and tags) providing important tools to support peptide drug discovery for different purposes:

  • Improve pharmacokinetic profiles
  • Modification/derivatization onto carriers for targeting and imaging approaches

Peptide conjugates can be designed and manufactured using a wide variety of linkages, including thiol-thiol, thioether, oximes, amine-thiol crosslinks, triazoles, and hydrazides.

Each peptide component is manufactured to a high purity and the final conjugated product is purified by size exclusion chromatography and/or RP-HPLC and/or ion exchange to generate a clean, well-characterized product by high resolution mass spectrometry techniques and/or MALDI/TOF.

Conjugation to Lipids and PEGs

Much of the focus for our discovery programs is on the conjugation of peptides to pharmacokinetics (PK)-enhancing moieties. The most common approach to improve PK properties relies on promoting the binding of peptide drugs to plasma proteins by conjugation of peptide leads with either fatty acids or cholesterol. Alternatively, PK profiles of peptides can be optimized by increasing the drug’s apparent molecular weight by conjugation with a polymer, such as polyethylene glycol (PEGs) to reduce renal filtration while protecting the peptide from proteolytic degradation.

Conjugation to Proteins, mAbs

Conjugation of peptides or proteins with other peptides, small molecules or tags can be performed for various purposes i.e. to promote an antigenic immune response, cellular uptake or receptor mediated drug delivery. The preferred method for linking a peptide to a carrier protein is through the side chain thiol (-SH) of a cysteine residue by means of maleimide chemistry, bromoacetylation or vynilsulfone in addition to site-specific derivatization.

Conjugation to Small Molecules (Fluorophores, chelating agents and therapeutics)

The team has extensive experience on the orthogonal and chemo-selective conjugation of synthetic peptides to a wide range of highly effective fluorescent markers, such as AlexaFluor®, Cy3, FITC, Biotin, and imaging agent precursors, such as DOTA and NOTA.

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