Improving oral bioavailability of peptides by multiple N-methylation: somatostatin analogues.

نویسندگان

  • Eric Biron
  • Jayanta Chatterjee
  • Oded Ovadia
  • Daniel Langenegger
  • Joseph Brueggen
  • Daniel Hoyer
  • Herbert A Schmid
  • Raz Jelinek
  • Chaim Gilon
  • Amnon Hoffman
  • Horst Kessler
چکیده

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Rational design and synthesis of an orally bioavailable peptide guided by NMR amide temperature coefficients.

Enhancing the oral bioavailability of peptide drug leads is a major challenge in drug design. As such, methods to address this challenge are highly sought after by the pharmaceutical industry. Here, we propose a strategy to identify appropriate amides for N-methylation using temperature coefficients measured by NMR to identify exposed amides in cyclic peptides. N-methylation effectively caps th...

متن کامل

On-resin N-methylation of cyclic peptides for discovery of orally bioavailable scaffolds

Backbone N-methylation is common among peptide natural products and has a substantial impact on both the physical properties and the conformational states of cyclic peptides. However, the specific impact of N-methylation on passive membrane diffusion in cyclic peptides has not been investigated systematically. Here we report a method for the selective, on-resin N-methylation of cyclic peptides ...

متن کامل

The effect of N-methylation of amino acids (Ac-X-OMe) on solubility and conformation: a DFT study.

N-Methylation has a significant impact on improving the oral bioavailability, lipophilicity and aqueous solubility of peptide-based lead drug structures. The selected mono-amino acid derivatives Ac-X-OMe, where X = Gly, Val, Leu, Ile, Phe, Met, Cys, Ser, Asp and His as well as their corresponding N-methylated analogues were studied. The clog P values of all N-methylated peptides are greater tha...

متن کامل

Somatostatin analogues in the treatment of gastroenteropancreatic neuroendocrine tumours, current aspects and new perspectives

Gastroenteropancreatic neuroendocrine tumours (GEP NETs) are rare tumours that present many clinical features.They secrete peptides and neuroamines that cause distinct clinical syndromes, including carcinoid syndrome. However, many are clinically silent until late presentation with mass effects.In 2000 the WHO developed a new classification which gives a better description of the characteristic...

متن کامل

Peptide receptor radionuclide therapy.

On their plasma membranes, cells express receptor proteins with high affinity for regulatory peptides, such as somatostatin. Changes in the density of these receptors during disease, for example, overexpression in many tumors, provide the basis for new imaging methods. The first peptide analogues successfully applied for visualization of receptor-positive tumors were radiolabeled somatostatin a...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Angewandte Chemie

دوره 47 14  شماره 

صفحات  -

تاریخ انتشار 2008