Name: Fmoc-Ala-Ala-PAB
Brand: BOC Sciences
Rating: 5 (1 reviews)

Synonyms

{(S)-1-[(S)-1-(4-Hydroxymethyl-phenylcarbamoyl)-ethylcarbamoyl]-ethyl}-carbamic acid 9H-fluoren-9-ylmethyl ester

IUPAC Name

9H-fluoren-9-ylmethyl N-[(2S)-1-[[(2S)-1-[4-(hydroxymethyl)anilino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]carbamate

Canonical SMILES

CC(C(=O)NC1=CC=C(C=C1)CO)NC(=O)C(C)NC(=O)OCC2C3=CC=CC=C3C4=CC=CC=C24

InChI

InChI=1S/C28H29N3O5/c1-17(27(34)31-20-13-11-19(15-32)12-14-20)29-26(33)18(2)30-28(35)36-16-25-23-9-5-3-7-21(23)22-8-4-6-10-24(22)25/h3-14,17-18,25,32H,15-16H2,1-2H3,(H,29,33)(H,30,35)(H,31,34)/t17-,18-/m0/s1

InChIKey

WFJHIWKUWIKWLW-ROUUACIJSA-N

Fmoc-Ala-Ala-PAB is an innovative cleavable linker commonly utilized in the creation of antibody-drug conjugates (ADCs), a class of targeted cancer therapies designed to deliver cytotoxic agents specifically to cancer cells while sparing healthy tissue. This linker is a compound structure consisting of a fluorenylmethyloxycarbonyl (Fmoc) group and an alanine-alanine (Ala-Ala) dipeptide spacer connected to a para-aminobenzyloxycarbonyl (PAB) moiety. Its carefully engineered structure allows for precise drug release in response to specific intracellular conditions, which is critical for reducing systemic toxicity and improving therapeutic efficacy. The Fmoc group offers facile removal and modification properties crucial during the synthesis phase, enabling better manipulation and integration of the linker into larger molecular frameworks.

The mechanism by which Fmoc-Ala-Ala-PAB operates is primarily through enzymatic cleavage within the cellular environment. Upon the ADC’s internalization into the target cancer cell, specific intracellular enzymes, such as cathepsins, recognize and cleave the Ala-Ala portion. This cleavage prompts the subsequent degradation of the PAB moiety, facilitating the release of the attached cytotoxic drug. This enzyme-triggered release mechanism ensures that the drug is only activated in the presence of its intended target, thereby maintaining a high therapeutic index and minimizing collateral damage to healthy cells. This specificity is vital in oncological applications where selective targeting can significantly affect treatment outcomes.

In drug discovery and development, Fmoc-Ala-Ala-PAB is pivotal due to its adaptability and efficiency. Its utilization allows for the synthesis of ADCs with improved pharmacokinetic and pharmacodynamic profiles. By employing this linker, researchers can create more versatile therapeutic agents capable of targeting a wide range of tumor antigens. Moreover, the modular nature of Fmoc-Ala-Ala-PAB offers significant advantages in adjusting linker-drug ratios and chemically modifying payloads to meet diverse therapeutic needs. This adaptability not only enhances the drug’s targeting efficiency but also provides pathways for overcoming resistance mechanisms that often arise during cancer treatments.

The importance of Fmoc-Ala-Ala-PAB in targeted drug delivery extends beyond its primary use in ADCs. It serves as a model for developing other cleavable linkers that can respond to varying physiological triggers within the body. Its design principles have informed the creation of linkers that respond to different biological stimuli, such as pH changes and redox conditions, which are key features of the tumor microenvironment. Through these innovations, Fmoc-Ala-Ala-PAB helps pave the way for more advanced drug delivery systems, impacting new therapies for various diseases including autoimmune disorders and infectious diseases.