In the field of amino acid derivatives, we introduced Smoc amino acids as product highlight for solid-phase peptide synthesis using water instead of organic solvents. In addition, the 2,7-disulfo-9-fluorenylmethoxycarbonyl (Smoc) N-term protecting group equips the respective amino acids with a pronounced fluorescence allowing for real-time monitoring during peptide synthesis. For all details, watch the recording of our workshop! 

Besides, we extended our amino acid portfolio by several Aloc-D-amino acids. 

Speaking of peptide synthesis, we also presented reagents and building blocks useful for the generation of larger peptides via ligation, such as the cyanylating reagent NTCB (RL-4080) as well as various selenocysteines as well as selenazolidine carboxylic acids, which can be deprotected into Sec by treatment with MeONH₂ at pH 4. Click here for more details! Besides, feel free to check-out or brochure “Ligation Technologies”! 

Concerning the field of life sciences, we would like to highlight His Tags for the Chemical Modification of Peptides. Jensen et al. developed two methods that use poly-His sequences to direct the highly selective acylation of proteins, either at the N-terminus or at a specific Lys residue. In addition, for site-specific protein labeling, we added several Substrates for Fusion (Halo/Snap/Clip)-Tagged Proteins. 

Regarding our Linkerology® portfolio, we would like to highlight our PROTAC® section. The “cell-own degradation machinery” can be recruited to targeted disease-related proteins via Proteolysis Targeting Chimeras (PROTACs®) allowing directed protein degradation. To construct and proof a suitable PROTAC®, Iris Biotech offers a variety of E3 ubiquitin ligase ligands and negative controls, e.g. Thalidomide, Pomalidomide and Lenalidomide, as well as carboxy-, click- and thiol-reactive linker-tagged E3 ubiquitin ligase ligands. 

Interested in different linker technologies, e.g. permanent/cleavable linkers? See our brochure Linkerology®.

You are looking for a different building block or special functionalization or spacer length not listed in our portfolio? Get in contact for a Custom Synthesis or browse our brochure to get an overview about our capabilities! 

References:

Sustainable Peptide Synthesis Enabled by a Transient Protecting Group; S. Knauer, N. Koch, C. Uth, R. Meusinger, O. Avrutina, H. Kolmar; Angew. Chem. Int. Ed. Engl. 2020; 59(31): 12984-12990. https://doi.org/10.1002/anie.202003676

WO2016 050764

Expressed Protein Ligation without Intein; Y. Qiao, G. Yu, K. C. Kratch, X. Aria Wang, W. Wei Wang, S. Z. Leeuwon, S. Xu, J. S. Morse, W. Ray Liu; J. Am. Chem. Soc. 2002; 142: 7057-7054. https://doi.org/10.1021/jacs.0c00252

Site-Specific Conversion of Cysteine in a Protein to Dehydroalanine Using 2-Nitro-5-thiocyanatobenzoic Acid; Y. Qiao, G. Yu, S. Z. Leeuwon, W. Ray Liu; Molecules 2021; 26: 2619. https://doi.org/10.3390/molecules26092619

Accelerated Protein Synthesis via One-Pot Ligation-Deselenization Chemistry; N. J. Mitchell, J. Sayers, S. S. Kulkarni, D. Clayton, A. M. Goldys, J. Ripoll-Rozada, P. J. Barbosa Pereira, B. Chan, L. Radom, R. J. Payne; Chem 2017; 2: 703-715. https://doi.org/10.1016/j.chempr.2017.04.003

Oxidative Deselenization of Selenocysteine: Applications for programmed Ligation at Serine; L. R. Malins, N. J. Mitchell, S. McGowan, R. J. Payne; Angew. Chem. Int. Ed. Engl. 2015; 54: 12716-12721. https://doi.org/10.1002/anie.201504639

Chemical Synthesis of Proteins with Non-Strategically Placed Cysteines Using Selenazolidine and Selective Deselenization; P. S. Reddy, S. Dery, N. Metanis; Angew. Chem. Int. Ed. 2016; 55(3): 992-995. https://doi.org/10.1002/anie.201509378

Copper-Mediated Deprotection of Thiazolidine and Selenazolidine Derivatives Applied to Native Chemical Ligation; N. Naruse, D. Kobayashi, K. Ohkawachi, A. Shigenaga, A. Otaka; J. Org. Chem. 2020; 85(3): 1425-1433. https://doi.org/10.1021/acs.joc.9b02388   

Chemical synthesis of proteins using peptide hydrazides as thioester surrogates; J. S. Zheng, S. Tang, Y. K. Qi, Z. P. Wang, L. Liu; Nat Protoc 2013; 8: 2483-2495. https://doi.org/10.1038/nprot.2013.152

Convenient method of peptide hydrazide synthesis using a new hydrazone resin; P. S. Chelushkin, K. V. Polyanichko, M. V. Leko, M. Y. Dorosh, T. Bruckdorfer, S. V. Burov; Tetrahedron Letters 2015; 56: 619-622. https://doi.org/10.1016/j.tetlet.2014.12.056

Leveraging the Knorr Pyrazole Synthesis for the Facile Generation of Thioester Surrogates for use in Native Chemical Ligation; D. T. Flood, J. C. J. Hintzen, M. J. Bird, P. A. Cistrone, J. S. Chen, P. E. Dawson; Angew Chem Int Ed Engl 2018; 57: 11634-11639. https://doi.org/10.1002/anie.201805191

Protein chemical synthesis by ligation of peptide hydrazides; G. M. Fang, Y. M. Li, F. Shen, Y. C. Huang, J. B. Li, Y. Lin, H. K. Cui, L. Liu; Angew Chem Int Ed Engl 2011; 50: 7645-7649. https://doi.org/10.1002/anie.201100996

Selective N-terminal acylation of peptides and proteins with a Gly-His tag sequence; M. C. Martos-Maldonado, C. T. Hjuler, K. K. Sorensen, M. B. Thygesen, J. E. Rasmussen, K. Villadsen, S. R. Midtgaard, S. Kol, S. Schoffelen, K. J. Jensen; Nat Commun 2018; 9: 3307. https://doi.org/10.1038/s41467-018-05695-3

Selective Acylation of Proteins at Gly and Lys in His Tags; K. J. Jensen, M. B. Thygesen, K. K. Sørensen, S. Wu, T. Treiberg, S. Schoffelen; ChemBioChem 2022. https://doi.org/10.1002/cbic.202200359

Site-specific protein labeling with SNAP-Tags; N. B. Cole; Curr Protoc Protein Sci. 2013; 73(30): 1-30. https://doi.org/10.1002/0471140864.ps3001s73

A general method for the covalent labeling of fusion proteins with small molecules in vivo; A. Keppler, S. Gendrezig, T. Gronemeyer, H. Pick, H. Vogel, K. Johnsson; Nat. Biotechnol. 2003; 21: 86-89. https://doi.org/10.1038/nbt765

HaloTag technology: a versatile platform for biomedical applications; C. G. England, H. Luo and W. Cai; Bioconjug Chem 2015; 26: 975-86. https://doi.org/10.1021/acs.bioconjchem.5b00191

Targeted protein degradation: mechanisms, strategies and application; L. Zhao, J. Zhao, K. Zhong, A. Tong, D. Jia; Signal Transduction and Targeted Therapy 2022; 7(113). https://doi.org/10.1038/s41392-022-00966-4

Recent Developments in PROTAC-Mediated Protein Degradation: From Bench to Clinic; Z. Hu, C. M. Crews; ChemBioChem 2022; 23(2). https://doi.org/10.1002/cbic.202100270