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Auristatins (1)

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Auristatins are a family of complex analogues to the native antineoplastic product dolastatin 10. They are 100 to 1000 times more toxic than Doxorubicin, a conventional cancer chemotherapy medication. – PowerPoint PPT presentation

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Title: Auristatins (1)


1
Auristatins
2

As one major component of an antibody-drug
conjugate (ADC), the antibody is the key for
target specificity and serves as the cargo to
deliver the cytotoxic drug (payload). A payload
drug can be attached to different sites on an
antibody using diverse conjugation chemistry.
Multiple endogenous amino acids can serve as
potential conjugation sites. However, to achieve
more precisely controlled site-directed
conjugations and subsequently a narrower
distribution of drug-to-antibody ratio (DAR),
special moieties with unique conjugation
chemistries are engineered into antibody
sequences in our antibody design services.
3

Antibody Design and Conjugation Some endogenous
or engineered sites for the conjugation of
cytotoxic payload drugs to an antibody
(Antibodies,2015).
4

To retain antibody bioactivity, mild,
near-physiological conditions are often used for
conjugation reactions. Under these conditions,
endogenous amino acids such as Lys and Cys are
chemically reactive and can be used as
conjugation sites. Scientists at Creative Biolabs
are experienced in performing Lysine conjugation
(amine reaction) as well as Cysteine conjugation
(thiol reactions) to create ADCs using these
endogenous sites. We are also expertise in
exploiting Tyrosine conjugation approaches as
another innovated endogens site for ADC
development.
5

One downside in using the endogenous amino acids
for ADC development is a heavily dispersed
drug-to-antibody ratio (DAR) caused by the
non-uniform distribution of the conjugation
sites, especially in the case of Lysine-based
conjugations.
6

Engineered/non-engineered antibodies are
conjugated to the corresponding drug-linker set
designed and prepared in DrugLnk and purified via
suitable liquid chromatography techniques. The
resulted ADCs are characterized for some basic
biochemical parameters such as DAR, stability,
conjugation site distribution.
7

Designing a chemically compatible antibody for
the conjugation chemistry is a key step that
directly dictates the fate of an ADC project.
With expertise and dedication, advanced antibody
design platform and services from Creative
Biolabs will be your best companion in creating
customized ADCs.
8
About
  • After years of pursuit for perfection, Creative
    Biolabs has established our leadership in
    targeted immunotherapy and antibody-drug
    conjugate (ADC) development. Creative Biolabs
    offers customers with comprehensive one-stop-shop
    of all aspects in ADC research and evaluation,
    ranging from antigen selection, antibody
    production/optimization, payload-linker
    synthesis, ADC conjugation, to various stages of
    ADC characterization and pre-clinical evaluation.
    Furthermore, inventory also contains an extensive
    list of linkers, payloads, payload-linker sets,
    and commonly used ADCs for quick deployment and
    concept validation.

9
Contact
  • 45-1 Ramsey Road, Shirley, NY 11967, USA
  • Email marketing_at_creative-biolabs.com
  • www.creative-biolabs.com/car-t

10
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