A Protease‐Based Strategy for the Controlled Release of Therapeutic Peptides

Li, Hongjian; Ma, Yi; Chen, Ying; Sang, Yanxia; Zhou, Tianhong; Qiu, Meilan; Huang, Xueling; Zhou, Cindy; Su, Zhengding

doi:10.1002/anie.201000287

Cited by 18 publications

(15 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, affinity of both two XTS1 peptides for monkey serum were obvious higher than mouse, rat and similar to human, indicating that pharmacokinetics parameters of XTS1 or XTS2 peptides in monkey were more closely to that in human compared with other species. Compared to the previous albumin binding affinity results, 21 stringing SEQ1 and SEQ2 exert almost ten-fold higher affinity for HSA than the single SEQ1 or SEQ2 (1.41 Â 10 À7 M vs. 1.12 Â 10 À6 M or 1.67 Â 10 À6 M).…”

Section: Albumin Binding Affinitycontrasting

confidence: 83%

“…The newly designed fusion peptides (termed XTS1 and XTS2) were comprised of an ABD, a linker with a cleavage site of TBN and a GLP-1(A8Aib). Compared with the previous reports, 21 we particularly enhanced the albumin-binding ability of XTS peptides by stringing two albumin binding peptides, and the 8th alanine was changed to 2-aminoisobutyric acid, a non-natural amino acid with outstanding resistance to DPP-IV, to improve the in vivo stability of the released GLP-1. 15 In this study, we prepared XTS peptides using a traditional solid phase synthesizing method and the obtained peptides were further identied using HPLC and mass spectrometry.…”

Section: Discussionmentioning

confidence: 96%

“…Thereby the peptide drugs, association tightly with serum albumin, will have longer in vivo half-lives compared with the unbound ones. 19,20 Based on the previous research, 21 our strategy for half-life extension was focused on the fusion of peptide drugs with albumin binding peptides that display high affinity for albumins. But the reported results indicated that these fusion peptides, containing only single albumin binding domain, exert only about an affinity of $1 mM for HSA, and the sequence of released natural GLP-1 includes DPP-IV digestion site, both of which leading to a short in vivo half-life (no more than 12 hours).…”

Section: Introductionmentioning

confidence: 99%

“…When our newly design fusion peptides were subcutaneously administrated into the blood circulation, they will rapidly bind to the albumin which can protect them from elimination action from kidney and proteolytic degradation. [21][22][23] The protease-cleavable linker will be consequentially scissile to TBN hydrolysis and release the mutated GLP-1(A8Aib) (Scheme 1).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Engineering an enhanced thrombin-based GLP-1 analog with long-lasting glucose-lowering and efficient weight reduction

Pan

Xie²,

et al. 2019

RSC Adv.

View full text Add to dashboard Cite

show abstract

Section: Albumin Binding Affinitycontrasting

confidence: 83%

Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Engineering an enhanced thrombin-based GLP-1 analog with long-lasting glucose-lowering and efficient weight reduction

Pan

Xie²,

et al. 2019

RSC Adv.

View full text Add to dashboard Cite

show abstract

“…However, as existing designs employed protease sites that are rapidly cleaved, these constructs still required repeated daily injections. Others have demonstrated release of serum albumin-bound peptides by thrombin-cleavable linkers, enabling once-a-day injection regimens 22. To further prolong the sustained release of peptide drugs, we sought to generate protease-responsive protein-polymers of a model peptide drug, GLP-1, with intervening thrombin cleavable sequences of variable strengths to optimize monomer release.…”

mentioning

confidence: 99%

A highly parallel method for synthesizing DNA repeats enables the discovery of ‘smart’ protein polymers

Amiram¹,

Quiroz²,

Callahan³

et al. 2011

Nature Mater

View full text Add to dashboard Cite

Robust high-throughput synthesis methods are needed to expand the repertoire of repetitive protein-polymers for different applications. To address this need, we developed a new method, overlap-extension rolling circle amplification (OERCA), for the highly parallel synthesis of genes encoding repetitive protein-polymers. OERCA involves a single PCR-type reaction for the rolling circle amplification of a circular DNA template and simultaneous overlap extension by thermal cycling. We characterized the variables that control OERCA and demonstrated its superiority over existing methods, its robustness, throughput and versatility by synthesizing variants of elastin-like polypeptides (ELPs) and protease-responsive polymers of a glucagon-like peptide-1 analog. Despite the GC-rich, highly repetitive sequences of ELPs, we synthesized remarkably large genes without recursive ligation. OERCA also enabled us to discover “smart” biopolymers that exhibit fully reversible thermally responsive behavior. This powerful strategy generates libraries of repetitive genes over a wide and tunable range of molecular weights in a “one-pot” parallel format.

show abstract

Delivery of Intact Transcription Factor by Using Self‐Assembled Supramolecular Nanoparticles

et al. 2011

View full text Add to dashboard Cite

Protein delivery [1] has been considered as the most straightforward strategy for modulating cellular behavior without the safety concerns and expression performance issues associated with gene deliver approaches. Two major challenges remain to be overcome in order to enable practical applications in biology and medicine 1) how to foster cellular uptake of protein molecules and 2) how to retain their stabilities and functions [2] over the delivery process. Recently, attempts have been made to develop a variety of delivery vectors, including liposomes, [3] polymer micelles, [4] and nanoparticle, [5] to enhance the uptake of protein molecules in target cells, and at the same time, to stabilize the encapsulated proteins. Owing to the time-consuming procedures employed in optimization of delivery materials, significant endeavors have been made in search of better delivery systems, although there has been limited progress in the field to date. Alternatively, recombinant technology [6] can be utilized to conjugate cell-penetrating peptides [7] (CPPs) onto protein molecules, this is the most commonly used protein delivery system with improved delivery efficiency. In this case, the major bottlenecks associated with the complicated procedure of generating recombinant proteins and the lack of protection mechanism against protein denature need to be solved.Transcription factor (TF) is a protein responsible for regulating gene transcription in cellular circuitry. [8] In general, TFs contain one or more DNA-binding domains (DBDs), which recognize matching DNA sequences adjacent to the genes they regulate. Apparently, highly efficient delivery of TFs can provide a powerful technology for modulating cellular behavior. One of the most important in-vitro applications that required highly efficient TF delivery is the generation of human induced pluripotent stem cells (hiPSCs) which has recently been demonstrated by introducing CPPsfused reprogramming TFs (i.e., OCT4, SOX2, KLF4, and c-MYC) [9] into human somatic cells. The resulting hiPSCs have the potential to revolutionize regenerative medicine.[10] However, the high costs of the four reprogramming TFs in their recombinant forms, means it is unlikely that this approach can be used for large-scale hiPSCs generation without further improvement in the delivery performance of the reprogramming proteins. Therefore, it is crucial to develop a new type of vector capable of delivering intact (unmodified) TFs in a highly efficient manner.Previously, we demonstrated a convenient, flexible, and modular self-assembly approach for the preparation of supramolecular nanoparticles (SNPs) from a small collection of molecular building blocks through a multivalent molecular recognition based on adamantane (Ad) and b-cyclodextrin (CD) motifs. Such a self-assembly synthetic strategy enables control upon the sizes, surfaces chemistry, zeta potentials, and payloads of the resulting SNPs, which open up many interesting opportunities for biomedical applications, for example, positron emission tomogr...

show abstract

A Protease‐Based Strategy for the Controlled Release of Therapeutic Peptides

Cited by 18 publications

References 29 publications

Engineering an enhanced thrombin-based GLP-1 analog with long-lasting glucose-lowering and efficient weight reduction

Engineering an enhanced thrombin-based GLP-1 analog with long-lasting glucose-lowering and efficient weight reduction

A highly parallel method for synthesizing DNA repeats enables the discovery of ‘smart’ protein polymers

Delivery of Intact Transcription Factor by Using Self‐Assembled Supramolecular Nanoparticles

Contact Info

Product

Resources

About