Sarcosine, also known as N-methylglycine, is a non-proteinogenic amino acid and represents an intermediate and byproduct in glycine synthesis and degradation. It was named and first isolated by the German chemist Justus von Liebig in 1847.

Iris Biotech offers various Sarcosine building blocks suitable for solid-phase peptide synthesis (SPPS) and for the synthesis of poly-Sarcosines (pSars). Our portfolio includes unprotected and protected (Fmoc, Boc, Z) Sarcosines (see related products) as well as a preformed protected bis-Sarcosine fragment (FAA7710) and a preloaded Fmoc-Sar-Wang Resin (WAA5132).

As a polymer, poly-Sarcosines show PEG like properties such as excellent solubility in water, protein resistance, low cellular toxicity and a non-immunogenic character and have thus gained increased attention within the last years.

For the synthesis of low molecular weight poly-Sarcosines, SPPS is a suitable method of choice. SPPS was invented in the 1960s by Merrifield. Thereby, the chain growth is conducted in a stepwise manner on a functionalized solid support. In a final step, the full-length construct is cleaved off the solid phase. Such synthesized monodisperse pSars are reported in literature for example for the construction of ADCs. The inclusion of the hydrophilic pSar moiety resulted in significant reduction of the ADC’s hydrophobicity level, associated with improved physicochemical and pharmacological properties.

Chemical structure of drug linker Exa-PSAR10 as reported in literature.

As synthetic alternative, for polymerization or the preparation of block copolymers, the Sar-N-carboxy anhydride (Sar-NCA) or Sar-N-thiocarboxy anhydride (Sar-NTA) can be synthesized as starting materials. Typically, the polymerization is then initiated by the ring-opening of the Sar-NCA/Sar-NTA upon nucleophilic attack. In comparison, one key advantage of NTAs over NCAs is their reduced reactivity leading to increased stability towards moisture and heat. However, Lu et al. recently reported a moisture- and air-tolerant route to unprotected NCAs.

N-carboxy anhydride synthesis via classical Fuchs-Farthing route.

Exemplary synthetic procedure for the synthesis of sarcosine N-thiocarboxy anhydrides.

➔ For more information on the benefits of poly-Sarcosines over PEGs, see one of our recent blogs. 

➔ Interested in pSars for the delivery of nucleic acids? Read on! 

References:
Exatecan Antibody Drug Conjugates Based on a Hydrophilic Polysarcosine Drug-Linker Platform; L. Conilh, G. Fournet, E. Fourmaux, A. Murcia, E.-L. Matera, B. Joseph, C. Dumontet, W. Viricel; Pharmaceuticals 2021; 14(3): 247. https://doi.org/10.3390/ph14030247.

Ligand-drug-conjugate comprising a single molecular weight polysarcosine. Viricel Warren; PCT Int. Appl. 2019; WO 2019081455 A1.

Polysarcosine-containing copolymers: Synthesis, characterization, self-asembly, and applications; A. Birke, J. Ling, M. Barz; Prog. Polym. Sci. 2018; 81: 163-208. https://doi.org/10.1016/j.progpolymsci.2018.01.002.

Synthesis and Characterization of Dendrimer-Based Polysarcosine Star Polymers: Well-Defined, Versatile Platforms Designed for Drug-Delivery Applications; R. M. England, J. I. Moss, A. Gunnarsson, J. S. Parker, M. B. Ashford; Biomacromolecules 2020; 21(8): 3332-3341. https://doi.org/10.1021/acs.biomac.0c00768.

Poly(sarcosine)-Based Nano-Objects with Multi-Protease Resistance by Aqueous Photoinitiated Polymerization-Induced Self-Assembly (Photo-PISA); S. Varlas, P. G. Georgiou, P. Bilalis, J. R. Jones, N. Hadjichristidis, R. K. O’Reilly; Biomacromolecules 2018; 19: 4453-4462. https://doi.org/10.1021/acs.biomac.8b01326.

Polysarcosine-Based Lipids: From Lipopolypeptoid Micelles to Stealth-Like Lipids in Langmuir Blodgett Monolayers; B. Weber, C. Seidl, D. Schwiertz, M. Scherer, S. Bleher, R. Süss, M. Barz; Polymers 2016; 8(12): 427. https://doi.org/10.3390/polym8120427.

Synthesis of polysarcosine from air and moisture stable N-phenoxycarbonyl-N-methylglycine assisted by tertiary amine base; A. Doriti, S. M. Brosnan, S. M. Weidner, H. Schlaad; Polym. Chem. 2016; 7: 3067-3070. https://doi.org/10.1039/C6PY00221H.

A moisture-tolerant route to unprotected alpha/beta-amino acid N-carboxyanhydrides and facile synthesis of hyperbranched polypeptides; Z.-Y. Tian, Z. Zhang, S. Wang, H. Lu; Nat. Commun. 2021; 12: 5810. https://doi.org/10.1038/s41467-021-25689-y.

An Inspection into Multifarious Ways to Synthesize Poly(Amino Acids)s; B. Zheng, T. Bai, X. Tao, J. Ling; Macromol. Rapid Commun. 2021; 42(22): 2100453. https://doi.org/10.1002/marc.202100453.