223741-66-0Relevant academic research and scientific papers
A Peptide Backbone Stapling Strategy Enabled by the Multicomponent Incorporation of Amide N-Substituents
Ricardo, Manuel G.,Marrrero, Javiel F.,Valdés, Oscar,Rivera, Daniel G.,Wessjohann, Ludger A.
supporting information, p. 769 - 774 (2019/01/04)
The multicomponent backbone N-modification of peptides on solid-phase is presented as a powerful and general method to enable peptide stapling at the backbone instead of the side chains. This work shows that a variety of functionalized N-substituents suitable for backbone stapling can be readily introduced by means of on-resin Ugi multicomponent reactions conducted during solid-phase peptide synthesis. Diverse macrocyclization chemistries were implemented with such backbone N-substituents, including the ring-closing metathesis, lactamization, and thiol alkylation. The backbone N-modification method was also applied to the synthesis of α-helical peptides by linking N-substituents to the peptide N-terminus, thus featuring hydrogen-bond surrogate structures. Overall, the strategy proves useful for peptide backbone macrocyclization approaches that show promise in peptide drug discovery.
LIBRARIES OF DIVERSE MACROCYCLIC COMPOUNDS AND METHODS OF MAKING AND USING THE SAME
-
Paragraph 0330; 0368; 0369, (2019/06/07)
The present disclosure relates to novel macrocyclic compounds and libraries thereof that are useful as research tools for drug discovery efforts. This disclosure also relates to methods of preparing these compounds and libraries and methods of using these libraries, such as in high throughput screening. In particular, these libraries are useful for evaluation of bioactivity at existing and newly identified pharmacologically relevant targets, including G protein-coupled receptors, nuclear receptors, enzymes, ion channels, transporters, transcription factors, protein-protein interactions and nucleic acid-protein interactions. As such, these libraries can be applied to the search for new pharmaceutical agents for the treatment and prevention of a range of medical conditions.
Tri-Orthogonal Scaffolds for the Solid-Phase Synthesis of Peptides
Pícha, Jan,Fabre, Benjamin,Budě?ínsky, Milo?,Hajduch, Jan,Abdellaoui, Mehdi,Jirá?ek, Ji?í
supporting information, p. 5180 - 5192 (2018/08/01)
Multi-orthogonal scaffolds can be useful for the attachment of several different compounds to the same central skeleton. Such compounds can find applications in the development of protein mimics because of their potential to mimic several distant epitopes
Orthogonal strategy for the synthesis of dual-functionalised β3-peptide based hydrogels
Kulkarni, Ketav,Motamed, Sepideh,Habila, Nathan,Perlmutter, Patrick,Forsythe, John S.,Aguilar, Marie-Isabel,Del Borgo, Mark P.
supporting information, p. 5844 - 5847 (2016/05/19)
We have described a new class of hydrogelator based on helical β3-peptides carrying a bioactive payload. The β3-peptides self-assemble in aqueous solution to form a nanofibrous mesh resulting in a stable hydrogel. The simple design provides the versatility for attaching different functional payloads to the β3-peptide scaffold to develop new materials.
Three-pronged probes: High-affinity DNA binding with cap, β-alanines and oligopyrrolamides
Haug, Ruediger,Kramer, Markus,Richert, Clemens
supporting information, p. 15822 - 15826 (2014/04/03)
TPP oligonucleotides: Hybridization probes that interrogate target sequences through base pairing, stacking on the terminus, and binding in the minor groove are presented (see figure). All subunits of the probes contribute to the target affinity, leading
Novel method for the synthesis of urea backbone cyclic peptides using new Alloc-protected glycine building units
Hurevich, Mattan,Tal-Gan, Yftah,Klein, Shoshana,Barda, Yaniv,Levitzki, Alexander,Gilon, Chaim
experimental part, p. 178 - 185 (2010/12/25)
Cyclization of bioactive peptides, utilizing functional groups serving as natural pharmacophors, is often accompanied with loss of activity. The backbone cyclization approach was developed to overcome this limitation and enhance pharmacological properties. Backbone cyclic peptides are prepared by the incorporation of special building units, capable of forming amide, disulfide and coordinative bonds. Urea bridge is often used for the preparation of cyclic peptides by connecting two amine functionalized side chains.Herewe present urea backbone cyclization as an additional method for the preparation of backbone cyclic peptide libraries. A straightforward method for the synthesis of crystalline Fmoc-Nα [ω-amino(Alloc)-alkyl] glycine building units is presented. A set of urea backbone cyclic Glycogen Synthase Kinase 3 analogs was prepared and assessed for protein kinase B inhibition as anticancer leads. Copyright
Expanding the scope and orthogonality of PNA synthesis
Pothukanuri, Srinivasu,Pianowski, Zbigniew,Winssinger, Nicolas
supporting information; experimental part, p. 3141 - 3148 (2009/05/27)
Peptide nucleic acids (PNAs) hybridize to natural oligonucleotides according to Watson and Crick base-pairing rules. The robustness of PNA oligomers and ease of synthesis have made them an attractive platform to encode small or macromolecules for microarr
Selective synthesis of carbamate protected polyamines using alkyl phenyl carbonates
Pittelkow, Michael,Lewinsky, Rasmus,Christensen, Jorn Bolstad
, p. 2195 - 2202 (2007/10/03)
Utilising alkyl phenyl carbonates, an economical, practical and versatile method for selective Boc, Cbz and Alloc protection of polyamines has been developed. This method allows Boc, Cbz and Alloc protection of primary amines in the presence of secondary amines by reaction of the polyamines with the alkyl phenyl carbonates. Also, this method allows mono carbamate protection of simple symmetrical aliphatic α,ω-alkanediamines in high yields with respect to the diamine. Finally, the method allows selective carbamate protection of a primary amine located on a primary carbon in the presence of a primary amine located on a secondary or a tertiary carbon in excellent yields.
Carbapenem antibacterial compounds, compositions containing such compounds and methods of treatment
-
, (2008/06/13)
Compounds of formula I are disclosed. as well as pharmaceutically acceptable salts thereof. The naphthosultam is substituted with various substituent groups including at least one cationic group -A-Q-L-B, wherein A-Q-L-B represents a side chain wherein: A is a C1-6alkylene group, straight or branched, and optionally interrupted or terminated by 1-2 of —O—, —S—, NRa—, —C(O)— and —CH═CH—; Q represents ?in which: b is 2 or 3; and X? is a charge balancing group; L represents a C1-8alkylene group, unsubstituted or substituted with 1-3 Rcgroups, and is interrupted or terminated by 1-3 of —CH═CH—, —C(O)—, —C(O)NRd—, —Het(Re)—, —C(O)—Het(Re)—, —C(O)NRa—Het(Re)—, —O—,—S—, —S(O)—, —SO2—, —CO2—, NRa—, —N+(Ra)2— B represents The carbapenems of the invention are effective against susceptible bacterial organisms, including methicillin resistant Staphylococcus aureus (MRSA), methicillin resistant Staphylococcus epidermidis (MRSE), and methicillin resistant coagulase negative Staphylococci (MRCNS).
