1. A screw, comprising:
a head, the head having an underhead bearing surface; and
a plurality of lubricant pockets, the lubricant pockets being arranged at least in a part of the underhead bearing surface.
2. The screw of claim 1, wherein the lubricant pockets are designed to be circumferentially closed as seen in cross-section.
3. The screw of claim 1, wherein the underhead bearing surface has a radial direction and a circumferential direction, the lubricant pockets being arranged to be distributed in an irregular way and that they are designed not to be continuous in the radial direction and in the circumferential direction of the underhead bearing surface.
4. The screw of claim 2, wherein the underhead bearing surface has a radial direction and a circumferential direction, the lubricant pockets being arranged to be distributed in an irregular way and that they are designed not to be continuous in the radial direction and in the circumferential direction of the underhead bearing surface.
5. The screw of claim 1, wherein the underhead bearing surface has a radial width, the lubricant pockets having an average diameter corresponding to approximately maximally 20% of the radial width of the underhead bearing surface.
6. The screw of claim 1, wherein the lubricant pockets have an average diameter of between approximately 50 to 500 \u03bcm.
7. The screw of claim 1, wherein the lubricant pockets have an average diameter of between approximately 100 to 300 \u03bcm.
8. The screw of claim 1, wherein the underhead bearing surface has an average surface roughness RZ of between approximately 10 to 100 \u03bcm for forming the lubricant pockets.
9. The screw of claim 1, wherein the underhead bearing surface has an average surface roughness RZ of between approximately 15 to 50 \u03bcm for forming the lubricant pockets.
10. The screw of claim 1, wherein the underhead bearing surface includes projecting portions and deepened portions, the deepened portions forming the lubricant pockets, the projecting portions being designed to be rounded and to have an average diameter of between approximately 50 to 500 \u03bcm.
11. The screw of claim 1, wherein the underhead bearing surface includes projecting portions and deepened portions, the deepened portions forming the lubricant pockets, the projecting portions being designed to be rounded and to have an average diameter of between approximately 100 to 300 \u03bcm.
12. The screw of claim 1, wherein the lubricant pockets are only arranged in a part of the underhead bearing surface.
13. The screw of claim 1, wherein the underhead bearing surface has radial outer part, the lubricant pockets only being arranged in the radial outer part.
14. The screw of claim 1, wherein the lubricant pockets are designed as cold formed lubricant pockets.
15. A washer for combination with a screw, the screw having a head including an underhead bearing surface, the washer comprising:
a first surface facing the underhead bearing surface of the screw; and
a plurality of lubricant pockets, the lubricant pockets being arranged at least in a part of the first surface.
16. The washer of claim 15, wherein the lubricant pockets are designed to be circumferentially closed as seen in cross-section.
17. The washer of claim 15, wherein the first surface has a radial direction and a circumferential direction, the lubricant pockets being arranged to be distributed in an irregular way and that they are designed not to be continuous in the radial direction and in the circumferential direction of the first surface.
18. The washer of claim 15, wherein the first surface has a radial width, the lubricant pockets having an average diameter corresponding to approximately maximally 20% of the radial width of the first surface.
19. The washer of claim 15, wherein the lubricant pockets have an average diameter of between approximately 50 to 500 \u03bcm.
20. The washer of claim 15, wherein the lubricant pockets have an average diameter of between approximately 100 to 300 \u03bcm.
21. The washer of claim 15, wherein the first surface has an average surface roughness RZ of between approximately 10 to 100 \u03bcm for forming the lubricant pockets.
22. The washer of claim 15, wherein the first surface has an average surface roughness RZ of between approximately 15 to 50 \u03bcm for forming the lubricant pockets.
23. A screw joint, comprising:
a component including a surface and a bore;
a screw having a head including an underhead bearing surface, the screw extending through the bore of the component;
a washer having a first surface and an opposite second surface, the washer being arranged between the underhead bearing surface of the screw and the surface of the component, the first surface of the washer of the underhead bearing surface of the screw and the second surface of the washer being arranged to face the surface of the component; and
a plurality of lubricant pockets, the lubricant pockets being arranged in at least a part of the underhead bearing surface of the screw.
24. The screw joint of claim 23, wherein a plurality of lubricant pockets is arranged at least in a part of the first surface of the washer.
25. The screw joint of claim 23, wherein the lubricant pockets are designed to be circumferentially closed as seen in cross-section.
26. The screw joint of claim 23, wherein the lubricant pockets have an average diameter of between approximately 50 to 500 \u03bcm.
27. The screw joint of claim 23, wherein the lubricant pockets have an average diameter of between approximately 100 to 300 \u03bcm.
28. A screw, comprising:
a head, the head having an underhead bearing surface, the underhead bearing surface having a radial direction, a circumferential direction and a radial width; and
a plurality of lubricant pockets containing lubricant,
the lubricant pockets being arranged at least in a part of the underhead bearing surface,
the lubricant pockets being arranged in an irregular way,
the lubricant pockets being designed not to be continuous in the radial direction and in the circumferential direction of the underhead bearing surface, and
the lubricant pockets having an average diameter of between approximately 50 to 500 \u03bcm and corresponding to approximately maximally 20% of the radial width of the underhead bearing surface.
29. The screw of claim 28, wherein the lubricant pockets are designed to be circumferentially closed as seen in cross-section.
30. The screw of claim 28, wherein the lubricant pockets are only arranged in a part of the underhead bearing surface.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1-19. (canceled)
20. A method for identifying peptide stabilizer compounds in vitro, comprising the steps of:
a) expressing a plurality of nucleic acid constructs, wherein each nucleic acid construct encodes a hybrid peptide that comprises:
i) a bioactive moiety; and
ii) a putative peptide stabilizer moiety;
b) exposing the expressed hybrid peptides to one or more proteases;
c) exposing the expressed hybrid peptides to a target molecule which is capable of interacting with the bioactive moiety in a detectable manner; and
d) if a detectable interaction occurs between a target molecule and the bioactive moiety of one or more of the expressed hybrid peptides, identifying said one or more expressed hybrid peptides as comprising a peptide stabilizer compound.
21. A method according to claim 20, further comprising the step of correlating the one or more expressed hybrid peptides of (d) with the corresponding nucleic acid constructs, thereby identifying nucleic acid sequences for the peptide stabilizer compounds.
22. A method according to claim 20, wherein steps (b) and (c) are carried out in the order of (c) then (b), or at the same time
23. A method according to claim 20, wherein the peptide stabilizer moiety comprises an amino acid sequence of between 2 and 20 residues in length.
24. A method according to claim 20, wherein the peptide stabilizer moiety comprises an amino acid sequence of between 2 and 20 residues in length, optionally modified at the N- or C-terminus or both; and its salts, derivatives and functional analogues thereof, wherein said derivatives and functional analogues may comprise naturally occurring or non-natural amino acids, peptide mimetics or peptide analogs.
25. A method according to claim 20, wherein the peptide stabilizer moiety is comprised within the bioactive moiety.
26. A method according to claim 20, wherein the bioactive moiety comprises one or more of the group consisting of: enzymes; hormones; cytokines; antibodies; antibody fragments; analgesics; antipyretics; anti-inflammatory agents; antibiotics; antiviral agents; anti-fungal drugs; cardiovascular drugs; drugs that affect renal function and electrolyte metabolism; drugs that act on the central nervous system; and chemotherapeutic drugs.
27. A peptide stabilizer compound identified by the method of claim 20.
28. A peptide stabilizer compound selected from the group consisting of HYPPPSTPYTTD (SEQ ID NO: 003); PTPTNPPQSAAD (SEQ ID NO: 004); ESPRPPARPPND (SEQ ID NO: 005); NHPTTNDGPSVK (SEQ ID NO: 006); PNRNFQQNTNHN (SEQ ID NO: 007); PATNPHTNSNAN (SEQ ID NO: 008); HNVNPNQPHNDT (SEQ ID NO: 009); VPTSTYAITDPT (SEQ ID NO: 010); PTMTRPSNTEAE (SEQ ID NO: 011); PTPSHSTHRDPE (SEQ ID NO: 012); HPHHPSNQAPTD (SEQ ID NO: 013); AAPDETTTPNRD (SEQ ID NO: 014); VNFAATSSNDRD (SEQ ID NO: 015); HDGRPPQHHHPH (SEQ ID NO: 016); MTMGTRPTRDTH (SEQ ID NO: 017); VNKQTTASQAHH (SEQ ID NO: 018); TNFSKDEQPTPD (SEQ ID NO: 019); GRPATAPCTHGN (SEQ ID NO: 020); DRSRASTRRDRH (SEQ ID NO: 021); SRHRTNAGETDH (SEQ ID NO: 022); ATGPIPHTPQGS (SEQ ID NO: 023); TDPPANDNAQPH (SEQ ID NO: 024); RFVSDHNITAAD (SEQ ID NO: 025); QPHNHPRPIKQH (SEQ ID NO: 026); ITPPDNSHTPDE (SEQ ID NO: 027); HGHSPSDNANTR (SEQ ID NO: 028); HCVHEPQTKHES (SEQ ID NO: 029); PSCPNKQDPTHD (SEQ ID NO: 030); TDCSHNPTDPCE (SEQ ID NO: 031); RAGELGAPADPD (SEQ ID NO: 032); and QKPNHDTERELD (SEQ ID NO: 033).
29. The peptide stabilizer compound of claim 28, which is optionally modified at the N- or C-terminus or both; and its salts, derivatives and functional analogues thereof, wherein said derivatives and functional analogues may comprise naturally occurring or non-natural amino acids, peptide mimetics or peptide analogs.
30. A biologically active peptide comprising a bioactive moiety and a peptide stabilizer compound selected from one or more of the peptide stabilizer compounds set out in claim 28.
31. A biologically active peptide according to claim 30, wherein the biologically active moiety is selected from the group consisting of: enzymes; hormones; cytokines; antibodies; antibody fragments; analgesics; antipyretics; anti-inflammatory agents; antibiotics; antiviral agents; anti-fungal drugs; cardiovascular drugs; drugs that affect renal function and electrolyte metabolism; drugs that act on the central nervous system; and chemotherapeutic drugs.
32. A pharmaceutical composition comprising at least one peptide stabilizer compound identified according to the method of claim 20, a bioactive molecule and a suitable carrier.
33. A pharmaceutical composition according to claim 32, wherein the peptide stabilizer compound is selected from the group consisting of: HYPPPSTPYTTD (SEQ ID NO: 003); PTPTNPPQSAAD (SEQ ID NO: 004); ESPRPPARPPND (SEQ ID NO: 005); NHPTTNDGPSVK (SEQ ID NO: 006); PNRNFQQNTNHN (SEQ ID NO: 007); PATNPHTNSNAN (SEQ ID NO: 008); HNVNPNQPHNDT (SEQ ID NO: 009); VPTSTYAITDPT (SEQ ID NO: 010); PTMTRPSNTEAE (SEQ ID NO: 011); PTPSHSTHRDPE (SEQ ID NO: 012); HPHHPSNQAPTD (SEQ ID NO: 013); AAPDETTTPNRD (SEQ ID NO: 014); VNFAATSSNDRD (SEQ ID NO: 015); HDGRPPQHHHPH (SEQ ID NO: 016); MTMGTRPTRDTH (SEQ ID NO: 017); VNKQTTASQAHH (SEQ ID NO: 018); TNFSKDEQPTPD (SEQ ID NO: 019); GRPATAPCTHGN (SEQ ID NO: 020); DRSRASTRRDRH (SEQ ID NO: 021); SRHRTNAGETDH (SEQ ID NO: 022); ATGPIPHTPQGS (SEQ ID NO: 023); TDPPANDNAQPH (SEQ ID NO: 024); RFVSDHNITAAD (SEQ ID NO: 025); QPHNHPRPIKQH (SEQ ID NO: 026); ITPPDNSHTPDE (SEQ ID NO: 027); HGHSPSDNANTR (SEQ ID NO: 028); HCVHEPQTKHES (SEQ ID NO: 029); PSCPNKQDPTHD (SEQ ID NO: 030); TDCSHNPTDPCE (SEQ ID NO: 031); RAGELGAPADPD (SEQ ID NO: 032); and QKPNHDTERELD (SEQ ID NO: 033).
34. A pharmaceutical composition according to claim 32, wherein the peptide stabilizer compound is selected from the group consisting of: HYPPPSTPYTTD (SEQ ID NO: 003); PTPTNPPQSAAD (SEQ ID NO: 004); ESPRPPARPPND (SEQ ID NO: 005); NHPTTNDGPSVK (SEQ ID NO: 006); PNRNFQQNTNHN (SEQ ID NO: 007); PATNPHTNSNAN (SEQ ID NO: 008); HNVNPNQPHNDT (SEQ ID NO: 009); VPTSTYAITDPT (SEQ ID NO: 010); PTMTRPSNTEAE (SEQ ID NO: 011); PTPSHSTHRDPE (SEQ ID NO: 012); HPHHPSNQAPTD (SEQ ID NO: 013); AAPDETTTPNRD (SEQ ID NO: 014); VNFAATSSNDRD (SEQ ID NO: 015); HDGRPPQHHHPH (SEQ ID NO: 016); MTMGTRPTRDTH (SEQ ID NO: 017); VNKQTTASQAHH (SEQ ID NO: 018); TNFSKDEQPTPD (SEQ ID NO: 019); GRPATAPCTHGN (SEQ ID NO: 020); DRSRASTRRDRH (SEQ ID NO: 021); SRHRTNAGETDH (SEQ ID NO: 022); ATGPIPHTPQGS (SEQ ID NO: 023); TDPPANDNAQPH (SEQ ID NO: 024); RFVSDHNITAAD (SEQ ID NO: 025); QPHNHPRPIKQH (SEQ ID NO: 026); ITPPDNSHTPDE (SEQ ID NO: 027); HGHSPSDNANTR (SEQ ID NO: 028); HCVHEPQTKHES (SEQ ID NO: 029); PSCPNKQDPTHD (SEQ ID NO: 030); TDCSHNPTDPCE (SEQ ID NO: 031); RAGELGAPADPD (SEQ ID NO: 032); and QKPNHDTERELD (SEQ ID NO: 033), wherein said peptide stabilizer is optionally modified at the N- or C-terminus or both; and salts, derivatives and functional analogues thereof, wherein said derivatives and functional analogues may comprise naturally occurring or non-natural amino acids, peptide mimetics or peptide analogs.
35. A pharmaceutical composition according to claim 32, wherein the bioactive molecule is selected from the group consisting of: enzymes; hormones; cytokines; antibodies; antibody fragments; analgesics; antipyretics; anti-inflammatory agents; antibiotics; antiviral agents; anti-fungal drugs; cardiovascular drugs; drugs that affect renal function and electrolyte metabolism; drugs that act on the central nervous system; and chemotherapeutic drugs.
36. A pharmaceutical composition according to claim 32, wherein the peptide stabilizer is attached to the bioactive molecule.
37. A pharmaceutical composition according to claim 32, wherein the peptide stabilizer is comprised within the bioactive molecule.
38. A pharmaceutical composition according to claim 32, wherein the composition is suitable for oral administration.
39. A method for imparting proteolysis resistance to a bioactive peptide molecule comprising, linking a peptide stabilizer compound identified by the method of claim 20 to the bioactive peptide molecule.
40. A method according to claim 39, wherein the peptide stabilizer compound is conjugated to the bioactive molecule.
41. A method according to claim 39, wherein the peptide stabilizer compound is genetically fused to the bioactive molecule.